Abstract: Current models of smoking and dependence assume a need to smoke at regular intervals to maintain nicotine levels, yet about 25% of adult smokers do not smoke daily. This subset of intermittent smokers (ITS) has gone largely unexamined. In this study, we describe the demographics, smoking history, and smoking behavior of ITS (n = 282; 50.2% male) in comparison to daily smokers (DS; n = 233; 60.7% male). Within ITS, we also compare "converted" ITS (CITS), who had previously smoked daily, with "native" ITS (NITS). On average, ITS were 34.66 years of age, and had smoked 42,850 cigarettes in the course of an average of 18 years of smoking. They smoked an average of 4.38 days per week, consuming 4.39 cigarettes a day on smoking days, and demonstrated considerable day-to-day variability in cigarette consumption. Almost half of ITS had Fagerstrom Test of Nicotine Dependence scores of 0, indicating no dependence. Compared to DS, ITS were more likely to cite alcohol drinking, socializing, and being with other smokers as common contexts for smoking, and they also more often cited being angry or stressed. Data suggested that ITS' behavior was not explained by use of other nicotine products nor by economic constraints on smoking, nor by differences in psychological adjustment. Within ITS, CITS were heavier, more frequent, and more dependent smokers. In many respects, CITS were intermediate between NITS and DS. ITS show distinct patterns of smoking behavior that are not well explained by current models of nicotine dependence.

Abstract: The consumption of alcohol mixed with energy drinks (AmED) has become a popular and controversial practice among young people. Increased rates of impaired driving and injuries have been associated with AmED consumption. The purpose of this study was to examine if the consumption of AmED alters cognitive processing and subjective measures of intoxication compared with the consumption of alcohol alone. Eighteen participants (nine men and nine women) attended four test sessions where they received one of four doses in random order (0.65 g/kg alcohol, 3.57 ml/kg energy drink, AmED, or a placebo beverage). Performance on a psychological refractory period (PRP) task was used to measure dual-task information processing and performance on the Purdue pegboard task was used to measure simple and complex motor coordination following dose administration. In addition, various subjective measures of stimulation, sedation, impairment, and level of intoxication were recorded. The results indicated that alcohol slowed dual-task information processing and impaired simple and complex motor coordination. The coadministration of the energy drink with alcohol did not alter the alcohol-induced impairment on these objective measures. For subjective effects, alcohol increased various ratings indicative of feelings of intoxication. More importantly, coadministration of the energy drink with alcohol reduced perceptions of mental fatigue and enhanced feelings of stimulation compared to alcohol alone. In conclusion, AmED may contribute to a high-risk scenario for a drinker. The mix of behavioral impairment with reduced fatigue and enhanced stimulation may lead AmED consumers to erroneously perceive themselves as better able to function than is actually the case.

Abstract: Binge drinking is a public health concern due to its association with negative health outcomes as well as increased legal and social consequences. Previous studies have frequently used self-reported alcohol consumption to classify binge drinking episodes; however, these measures are often limited in both detail and accuracy. Some researchers have begun using additional measures such as blood (BAC) and breath (BrAC) alcohol concentrations to supplement self-report data. Transdermal alcohol testing, or the detection of alcohol expiration through the skin, offers advantages over BAC and BrAC measures by allowing for continuous and noninvasive monitoring of an individual's drinking behavior in real time. Despite these advantages, this technology has not been widely used or studied outside of forensic applications. The present research compares transdermal alcohol concentration (TAC) and BrAC readings during the consumption of alcohol ranging from moderate drinking to binge drinking in 22 adult regular drinkers in order to investigate the sensitivity and specificity of the TAC monitors. We observed that BrAC and TAC measures were broadly consistent. Additionally, we were able to develop an equation that could predict BrAC results using TAC data, indicating TAC data would be an appropriate substitute in research and clinical contexts where BrAC readings are typically used. Finally, we were able to determine a cutoff point for peak TAC data that could reliably predict whether a participant had engaged in moderate or more-than-moderate drinking, suggesting TAC monitors could be used in settings where moderate or reduced drinking is the goal.

Abstract: Smoking is the leading cause of preventable death in the United States (Danaei et al., 2009). Although men are more likely to smoke than women (USDHS, 2010), women may be more sensitive to certain aspects of nicotine addition. For example, women are more sensitive to the subjective effects of nicotine (Myers, Taylor, Moolchan, & Heishman, 2008; Sofuoglu, Mitchell, & Mooney, 2009) and more likely to cite tension reduction, stimulation, social dynamics (Berlin et al., 2003), and appetite suppression as reasons for smoking (Reid, Pipe, Riley, & Sorensen, 2009). Smoking is associated with significant health risks in women (Perkins, 2001), and more women than men report having tried nicotine replacement therapy (NRT) to quit smoking (Reid, et al., 2009). However, women are less likely than men to achieve sustained abstinence following NRT (Bohadana, Nilsson, Rasmussen, & Martinet, 2003; Japuntich et al., 2011; Perkins, 2001). Ovarian hormones may contribute to gender differences in nicotine addiction. Estradiol is thought to enhance women’s sensitivity to nicotine, whereas progesterone is thought to be protective (Lynch & Sofuoglu, 2010). Tonic progesterone administration in the context of relatively low estradiol levels increases the subjective negative effects of nicotine, decreases the subjective positive effects of nicotine, and reduces the urge to smoke in women (Sofuoglu & Mooney, 2009). These findings are supported by experimental animal studies, which have demonstrated decreased motivation for nicotine when progesterone levels are high (Lynch, 2009). However, the effects of progesterone on smoking behavior in women are less clear (Sofuoglu, Babb, & Hatsukami, 2001; Sofuoglu, Mouratidis, & Mooney, 2011). The majority of research examining the effects of ovarian hormones on smoking has used menstrual cycle phase as a proxy for ovarian hormone function. These studies typically compare women in different phases of the menstrual cycle (e.g., follicular vs. luteal), and the results have been quite mixed. Some studies show increased smoking during menses (DeBon, Klesges, & Klesges, 1995; Marks, Hair, Klock, Ginsburg, & Pomerleau, 1994), others show increased smoking during the late-luteal phase (DeBon, et al., 1995; Snively, Ahijevych, Bernhard, & Wewers, 2000), and others show no relationship between cigarette smoking and menstrual phase (Allen, Hatsukami, Christianson, & Nelson, 1996; Allen, Hatsukami, Christianson, & Nelson, 1999; Pomerleau, Cole, Lumley, Marks, & Pomerleau, 1994). Certain methodological issues may have contributed to the inconsistent findings across studies. Previous studies used arbitrary phase classifications to denote differences in hormonal milieu. Comparisons of one phase vs. another (follicular vs. luteal) can be problematic to the extent that such phases are imperfect proxies of actual hormone levels because estradiol and progesterone levels fluctuate significantly within cycle phases (see Figure 1). Thus, the low absolute levels of estradiol and progesterone experienced during menses {DeBon, 1995 #116}{Marks, 1994 #149}, the decreasing levels of estradiol and progesterone experienced during the luteal-phase {DeBon, 1995 #116}{Snively, 2000 #113}, or the relative ratio of estradiol to progesterone (or vice versa) may be associated with increased smoking. The ratios of ovarian hormones (estradiol/progesterone or progesterone/estradiol) are associated with the exacerbation of a number of neurological and psychiatric conditions, including the frequency of seizures in women with epilepsy (Herzog, 1999), the number and volume of brain lesions associated with multiple sclerosis (Pozzilli et al., 1999), and menstrual distress in women with migraines (Beckham et al., 1992). Previous studies of smoking cessation have used the ratio of estradiol to progesterone rather than the reverse (Allen, Bade, Center, Finstad, & Hatsukami, 2008). Given that the two ratios (i.e., estradiol/progesterone and progesterone/estradiol) are not equivalent or linearly related, either or both ratios may be of importance. Thus, a more rigorous examination of hormonal influences on smoking behavior would focus on absolute and changing levels of both progesterone and estradiol, and the relationship between hormones (i.e., the ratio of progesterone to estradiol or vice versa). Figure 1 Approximate ovarian hormone levels during the menstrual cycle. A second methodological issue that may have contributed to previous discrepant findings is related to the assessment of smoking behaviors. Many previous studies have relied on self-reported smoking behavior occurring hours or days following the assessment of menstrual cycle phase or hormone levels, and this varying lag in time between predictor and outcome likely accounts for different conclusions. It is critical that assessments, hormones and smoking behaviors are temporally congruent in order to detect meaningful associations. Thus, laboratory assessment is advantageous because smoking behaviors can be examined in relation to hormones measured at the same time. The current study examines data from an ongoing smoking cessation trial to elucidate the relationship between ovarian hormones and smoking by directly measuring ovarian hormone levels and obtaining a detailed laboratory assessment of smoking behaviors. While it is difficult to derive a single, definitive hypothesis from the inconsistent findings noted above, we tentatively propose the following four hypotheses: increased smoking will be associated with 1) low levels of estradiol and progesterone; 2) decreasing estradiol and decreasing progesterone; 3) lower ratios of progesterone to estradiol; and 4) higher ratios of estradiol to progesterone.

Abstract: Impaired control over alcohol use may be defined as "a breakdown of an intention to limit consumption in a particular situation" (Heather, Tebbutt, Mattick, & Zamir, 1993, p. 701) and has long been considered an important feature of alcohol dependence. Evidence suggests impaired control is highly relevant to young adult problem drinking. In the natural history of problem drinking, impaired control tends to develop early and may predict alcohol-related problems prospectively in undergraduates. Impaired control over alcohol use may be a facet of generalized behavioral undercontrol specifically related to drinking. In particular, impaired control is theoretically and empirically related to impulsivity. The question of whether impaired control represents a facet of impulsivity or a related but separate construct requires further study. However, theoretical arguments and empirical evidence suggest that there are unique qualities to the constructs. Specifically, existing data suggest that self-report measures of impaired control and impulsivity over alcohol use relate distinctly to problem drinking indices in young adults. Several lines of future research concerning impaired control are suggested, using the impulsivity literature as a guide. We conclude that impaired control is a valuable construct to the study of young adult problem drinking and that measures of impaired control should be included in more young adult alcohol studies. The extent to which impaired control over the use of other substances and impaired control over engagement in other addictive behaviors are clinically relevant constructs requires additional study. (PsycINFO Database Record (c) 2011 APA, all rights reserved). Language: en

Abstract: When self-control resources are depleted ("ego depletion"), alcohol-seeking behavior becomes closely associated with automatic alcohol-related processing biases (e.g., Ostafin, Marlatt, & Greenwald, 2008). The current study aimed to replicate and extend these findings, and also to investigate whether the effects of ego depletion on drinking behavior would be mediated by temporary impairments in executive function or increases in impulsivity. Eighty heavy social drinkers (46 female) initially completed measures of automatic approach tendencies (stimulus response compatibility [SRC] task) and attentional bias (visual probe task) elicited by alcohol-related cues. Participants were then exposed to either an ego depletion manipulation or a control manipulation, before completing a bogus taste test in order to assess ad-lib alcohol consumption. In a subsequent testing session, we examined effects of the ego depletion manipulation (vs. control manipulation) on 3 aspects of executive function (inhibitory control, phonemic fluency, and delay discounting). Results indicated that the ego depletion manipulation increased ad-lib drinking, relative to the control manipulation. Automatic approach tendencies, but not attentional bias, predicted ad-lib drinking, although this effect was not moderated by ego depletion. Ego depletion had inconsistent effects on measures of executive function and impulsivity, and none of these measures mediated the effect of ego depletion on ad-lib drinking. However, the effect of ego depletion on ad-lib drinking was mediated by self-reported effort in suppressing emotion and thoughts during the manipulation. Implications for the effects of self-control strength on drinking behavior, and cognitive mediators of these effects, are discussed.

Abstract: Individual differences in drug dependence may be mediated by several abnormalities in associative learning, including perseveration of drug-seeking following contingency change, greater control over drug-seeking by Pavlovian stimuli, or greater sensitivity to drug reinforcement establishing higher rates of drug-seeking. To evaluate these three candidate markers for nicotine dependence, Experiment 1 contrasted daily (N = 22) and nondaily smoker groups (N = 22) on a novel instrumental learning task, where one S+ was first trained as a predictor of tobacco reward before being extinguished. Experiment 2 compared daily (N = 18) and nondaily smoker groups (N = 18) on a concurrent-choice task for tobacco and chocolate reward before an extinction test in which the tobacco response was extinguished, followed by a Pavlovian-to-instrumental transfer test, wherein the impact of tobacco and chocolate cues on concurrent choice was measured (gender was balanced within each smoker group). The results showed no group difference in sensitivity to extinction of either the stimulus-drug or response-drug contingency in Experiments 1 and 2, respectively, nor did groups show a difference in Pavlovian-to-instrumental transfer of control over tobacco choice. By contrast, nicotine-dependence status was marked by a higher frequency of tobacco choice in the concurrent-choice procedure, and this choice preference was associated with subjective craving (gender did not affect any behavioral measure). These results favor the view that nicotine dependence in this sample is not determined by individual predilection for perseveration or stimulus-control over drug-seeking, but by greater sensitivity to reinforcement of instrumental drug choice. Value-based decision theories of dependence are discussed.

Abstract: A behavioral economic approach to understanding the relative value of alcohol may be useful for advancing medication development for alcoholism. Naltrexone is a heavily researched and moderately effective treatment for alcohol dependence making it a good candidate for a proof-of-concept study of behavioral economics and alcoholism pharmacotherapy. This study examines naltrexone efficacy and pharmacogenetics in terms of the relative value of alcohol, assessed via demand curve analysis. Participants were 35 heavy drinking (AUDIT ≥8) Asian Americans. A within-subjects cross-over medication design was used along with an intravenous alcohol challenge completed after 4 days of both naltrexone and placebo. At baseline and BrAC = 0.06g/dl, participants completed an Alcohol Purchase Task, which assessed estimated alcohol consumption along escalating prices. Behavioral economic demand curve analysis yielded measures of intensity, elasticity, maximum expenditure (O(max)), proportionate price insensitivity (P(max)) and breakpoint. Compared to placebo, naltrexone significantly reduced intensity, O(max) and breakpoint. There were also trend-level medication effects on P(max). BrAC was associated with increases in P(max) and breakpoint. A significant naltrexone × OPRM1 genotype interaction was observed for intensity of demand. The present study extends the literature on naltrexone's mechanisms through the application of a novel behavioral economic paradigm. These results indicate that naltrexone reduces several indices of demand for alcohol. This preliminary report provides further evidence for the effectiveness of naltrexone and supports the utility of a behavioral economic approach to alcoholism pharmacotherapy development.

Abstract: Heavy drinking has increased in recent years and has been linked to numerous health-related risks, particularly in women. A number of factors may play a role in exacerbating the risks linked to heavy drinking, such as impulsivity, which itself is related to a number of risky behaviors. The present study investigated the effects of alcohol (0, 0.5, 0.75 g/kg) on impulsivity in female heavy drinkers (n = 23) and female light drinkers (n = 23) using a double-blind, placebo-controlled outpatient design; all women were tested during follicular phase of the menstrual cycle. Each session, participants completed a range of tasks including subjective measures of abuse liability, cognitive performance tasks, three behavioral impulsivity tasks, and a risk-taking task. Alcohol increased impulsivity on the Immediate and Delayed Memory Task (IMT and DMT) and Delay Discounting task. Heavy drinkers scored higher on impulsivity self-reports and were more impulsive on the IMT and the GoStop task than light drinkers. The high dose of alcohol further increased impulsive performance on the IMT and DMT in heavy drinkers. There were no group differences or alcohol effects on the Balloon Analogue Risk Task. Alcohol increased sedative-like effects more in light drinkers and increased stimulant-like effects and alcohol liking more in heavy drinkers. In summary, female heavy drinkers are less sensitive to the negative effects of alcohol, report more positive effects of alcohol, and are more impulsive than female light drinkers. Moreover, impulsive responding was exacerbated by alcohol drinking among female heavy drinkers, indicating that women who drink at this level are at increased risk for developing alcohol use disorders and engaging in other risky behaviors, particularly after drinking. (PsycINFO Database Record (c) 2012 APA, all rights reserved). Language: en

Abstract: Delay discounting is the decline in a consequence's control of behavior as a function of its delay, and may be a fundamental behavioral process in drug dependence. Human delay-discounting studies have usually relied on choices between hypothetical rewards. Some human tasks have assessed delay discounting using operant procedures with consequences provided during the task, as in nonhuman animal studies. However, these tasks have limitations such as long duration, potentially indeterminate data, or confounding the effect of delay with probability. A study in 20 cocaine-dependent volunteers and 20 demographically matched non-cocaine-dependent volunteers was designed to investigate a novel operant delay-discounting task providing monetary reinforcement by coin delivery throughout the task (Quick Discounting Operant Task; QDOT). Participants completed a hypothetical delay-discounting procedure, a potentially real reward delay-discounting procedure, and an existing operant delay-discounting task: the Experiential Discounting Task (EDT). The QDOT resulted in complete data for all participants, showed systematic effects of delay that were well described by a hyperbolic function, had a maximum duration of 17 min, and resulted in relatively little variability in session earnings. QDOT performance was significantly, positively correlated with performance on the EDT but not the other tasks. The QDOT resulted in an effect size between the groups that was similar to most other delay discounting tasks examined, and showed the cocaine-dependent participants to delay discount significantly more than the control participants. The QDOT is an efficient operant human delay-discounting task that may be useful in a variety of experimental settings.

Abstract: Social learning theory considers self-efficacy as a causal factor in behavior change. However, in line with behavioral theory, recent clinical research suggests self-efficacy ratings may reflect, rather than cause, behavior change. To test these two disparate views, self-efficacy was related to actual smoking abstinence on the next day (i.e., self-efficacy causes change), and abstinence status over 1 day was tested as a predictor of rated self-efficacy for quitting the next day (i.e., reflects change). All data were from two similar crossover studies evaluating the short-term effects of both placebo versus medication, nicotine patch (n = 209) or varenicline (n = 123), on smoking abstinence during week-long practice quit attempts. Placebo and active medication periods were separated by an ad lib smoking washout, and analyses were controlled for prior-day's abstinence or self-efficacy values. Results were very consistent between studies in showing essentially bidirectional associations: daily self-efficacy predicted next-day's abstinence, and current-day's abstinence status predicted self-efficacy for abstinence the next day. However, secondary factors differentially predicted abstinence and, to a lesser extent, self-efficacy, between these two medication studies. These data provide some support for both social learning and behavioral theories of smoking behavior change, although self-efficacy may only briefly predict subsequent short periods of abstinence as assessed in these studies. Nonetheless, because self-efficacy has long been assumed to cause behavior change, including smoking cessation, the notion of self-efficacy as a reflection of recent smoking behavior change in these studies warrants greater attention in clinical research on smoking cessation treatment.

Abstract: The influence of reinforcer magnitude and reinforcer delay on smoking abstinence was studied using an analog model of contingency management. Participants (N = 103, 74% men) visited our laboratory 3 times daily for 5 days and received money for providing a breath sample that indicated smoking abstinence (carbon monoxide level ≤6 parts per million). Using a factorial design, we assigned participants randomly to 1 of 4 groups that could earn a total of either $207.50 (high-magnitude condition) or $70.00 (low-magnitude condition), and received earnings either at each visit (no-delay condition) or in a single lump sum 1 week following the study (delay condition). High-magnitude reinforcement, regardless of delay, was associated with higher rates of abstinence than was low-magnitude reinforcement. High magnitude of reinforcement provided immediately but in incremental amounts was associated with longer intervals to relapse during treatment in comparison with high-magnitude reinforcement provided in a single lump sum after a delay. Low rates of responding in the low-magnitude conditions made interpretation of the impact of delay in those conditions difficult. These findings further demonstrate that high magnitude of reinforcement results in better outcomes than does low magnitude of reinforcement, and that a delay to reinforcement can be detrimental-even when a high magnitude of reinforcement is provided.

Abstract: Nicotine deprivation is associated with craving, negative affect, and difficulty concentrating, which may contribute to subsequent relapse. Bupropion and varenicline are both effective treatments for smoking cessation, and evidence from clinical trials suggests that these treatments increase abstinence rates. However, the mechanism by which these medications reduce relapse remains unclear. Recent research has focused on cognitive processes, such as attention and working memory, which may predict relapse. In addition, there may also be sex differences in cognitive-related deficits during nicotine deprivation. The current sample consisted of 58 (22 females) daily smokers (at least 10 cigarettes per day) randomized to receive bupropion (300 mg/day), varenicline (2 mg/day), or placebo. After a 1-week run-up phase, participants completed a 9.5-hr laboratory session after overnight abstinence (CO verified). Participants completed measures of attention (Conners’ Continuous Performance Task [CPT]), working memory (digits backward), and delay discounting. Measures of craving, withdrawal, and mood were also collected. Between-subjects ANCOVA models revealed that varenicline speeded reaction time, but reduced accuracy on the CPT compared with placebo. Sex moderated the effect of bupropion compared with placebo on working memory and delay discounting. Bupropion enhanced working memory for females but not males, and this pattern was reversed for delay discounting. The current data highlight the complex processes associated with nicotine deprivation and the need for future research to examine whether cognitive-related deficits are related to relapse. Identifying these mechanisms may help in the development of new pharmacological treatments.

Abstract: The cognitive influences of omega-3 polyunsaturated fatty acids (n-3 PUFA) remain unclear throughout the life span. Dietary n-3 PUFA appear cognitively beneficial prenatally and neuroprotective at later age; however, researchers using supplementation designs have reported disparate findings across age groups. Few studies have examined the cognitive impact of n-3 PUFA during young adulthood. This study assessed the cognitive effects of fish oil supplementation at college age, hypothesizing benefits on affect, executive control, inhibition, and verbal learning and memory. College-aged participants were assigned to active (n = 20, 5 men; age = 19.9, sage = 1.8) or placebo (n = 21, 7 men; age = 20.4, sage = 1.6) treatments, receiving fish oil (480 mg DHA/720 mg EPA) or coconut oil, respectively. Both groups completed four weeks of supplementation. At baseline and posttreatment, the researchers administered the Rey Auditory Verbal Learning Test (RAVLT; Lezak, 1995), Stroop Color and Word Test (SCWT; Golden & Freshwater, 2002), Trail Making Test (TMT; Corrigan & Hinkeldey, 1987; Gaudino, Geisler, & Squires, 1995; Lezak, 1995), and Positive and Negative Affect Schedule (PANAS; Watson, Clark, & Tellegen, 1988). Repeated-measures ANOVAs indicated no benefits of fish oil on the SCWT, RAVLT Stages 1 to 5, or PANAS. An interaction occurred between condition and time of measurement (i.e., baseline and posttreatment) on RAVLT Stages 6 and 7, and placebo significantly improved TMT performance over fish oil. The benefits of n-3 PUFA on RAVLT performance derived more from depreciated placebo performance than improved performance due to fish oil. The placebo gain on TMT performance likely derived from a learning effect. Together, these results present limited cognitive benefits of n-3 PUFA at college age; however, the treatment may have been subtherapeutic, with a larger sample needed to generalize these results.

Abstract: The extended-release formulation of zolpidem (Ambien CR®) is approved for the treatment of insomnia without a treatment duration limit. Acutely zolpidem impairs performance, and no research to date has examined whether tolerance develops to these performance impairments during nighttime awakening. The present double-blind, placebo-controlled study examined whether tolerance develops to zolpidem-induced acute performance impairment after repeated (22–30 days) nightly use. Effects of bedtime administration of zolpidem extended-release (ZOL; 12.5 mg) were tested on a battery of performance measures assessed during a forced nighttime awakening in 15 healthy male volunteers who completed overnight polysomnographic recording sessions in our laboratory at baseline and after approximately a month of at-home ZOL. As expected, bedtime ZOL administration was associated with changes in sleep architecture and impairments across all performance domains during nighttime testing (psychomotor function, attention, working memory, episodic memory, metacognition) with no residual next morning impairment. Tolerance did not develop to the observed ZOL-related impairments on any outcome. Possible evidence of acute abstinence effects following discontinuation of ZOL was observed on some performance and sleep outcomes. Overall, these findings suggest that performance is significantly impaired during nighttime awakening even after a month of nightly ZOL administration and these impairments could significantly impact safety should nighttime awakening require unimpaired functioning (e.g., driving; combat-related activities in the military).

Abstract: Previous studies have reported that exercise decreases cocaine self-administration in rats with long-term access (8+ weeks) to activity wheels in the home cage. The purpose of this study was to (a) examine the importance of the temporal relationship between physical activity and initial drug exposure, (b) determine the effects of exercise on responding maintained by a nondrug reinforcer (i.e., food), and (c) investigate the effects of exercise on cocaine-induced increases in locomotor activity. To this end, female rats were obtained at weaning and divided into 4 groups: (a) EXE-SED rats were housed in exercise cages for 6 weeks and then transferred to sedentary cages after the first day of behavioral testing; (b) SED-EXE rats were housed in sedentary cages for 6 weeks and then transferred to exercise cages after the first day of behavioral testing; (c) SED-SED rats remained in sedentary cages for the duration of the study; and (d) EXE-EXE rats remained in exercise cages for the duration of the study. Relative to the sedentary group (SED-SED), exercise reduced cocaine self-administration in both groups with access to activity wheels after initial drug exposure (EXE-EXE, SED-EXE) but did not reduce cocaine self-administration in the group with access to activity wheels only before drug exposure (EXE-SED). Exercise also decreased the effects of cocaine on locomotor activity but did not reduce responding maintained by food. These data suggest that exercise may reduce cocaine use in drug-experienced individuals with no prior history of aerobic activity without decreasing other types of positively reinforced behaviors.

Abstract: Impulsive behavior in heroin-dependent individuals and matched smokers was studied within the framework of temporal discounting. Two well-known effects were examined: the sign and magnitude effects (Kirby, 1997). The study also investigated the relationship between cognitive impulsivity and inhibitory control as measured by a Go/No-go task. Fifty-six heroin-dependent patients in the postmethadone treatment stage and an equal number of matched daily smokers participated in the study. The heroin-dependent patients showed higher discount rates in both gain and loss conditions. They also showed no sign effect by demonstrating similar discount rates in gains and losses. Heroin-dependent patients also exhibited a magnitude effect, which was weaker than that observed in smokers. Differential relationships between impulsivity and inhibitory control were found in the two groups. For smokers, decision-making and inhibitory control behaviors pertained to different psychological processes, whereas for heroin-dependent patients, the two behaviors were partially related. Finally, a significant correlation between length of heroin use and temporal discounting with small magnitude was found. The present study advances our understanding of the specific behavioral impulsive patterns in heroin-dependent individuals.

Abstract: Smoking/nicotine has been shown to increase brain arousal states, yet previous studies have failed to distinguish between absolute improvements due to nicotine versus relief from withdrawal symptoms in smokers. This study examined the electrocortical response to nicotine in a nonsmoking population, in order to negate potential withdrawal symptoms. Twenty right-handed, nonsmoking participants were administered nicotine (6 mg) or placebo gum within a double-blind, repeated-measures design. In each session, EEG was recorded during a 2-min, resting, eyes-open condition. Nicotine administration (vs. placebo) resulted in significantly greater frontal (specifically left-frontal) alpha2 power. Similar to previous findings in smokers. The absence of slow-wave changes following nicotine in nonsmokers suggest that these previous results in smokers may be related to withdrawal state.

Abstract: Regardless of actual nicotine content, expectations about the nicotine content of a cigarette influence the rewarding subjective effects of smoking, and may even affect cognitive performance. These effects are theorized to be mediated by beliefs about effects of cigarette smoking, or response expectancies. However, few studies have directly manipulated response expectancies. Understanding the effects of such manipulations could improve effectiveness of nicotine-dependence treatments and medications. Using a 2 × 2 between-subjects factorial design, cigarette smokers (N = 80) smoked either a nicotine or a placebo (denicotinized) cigarette crossed with instructions that the cigarette would either enhance or impair cognitive and motor performance. As predicted, participants in the "told enhance" condition reported significantly greater beliefs that nicotine had beneficial effects on performance than those in the "told impair" condition. Compared to those "told impair," those "told enhance" reported more psychological reward, enjoyable physical sensations, and craving reduction from the cigarette, as well as greater motivation to perform well on a cognitive task. Relative to placebo cigarettes, nicotine cigarettes produced greater reports of satisfaction, craving reduction, and dizziness. Smoking a nicotine cigarette produced better performance on the Rapid Visual Information Processing Task, a test of sustained attention; but the expectancy manipulation had no effect. These data suggest that response expectancies can be experimentally manipulated and can influence perceived rewarding effects of cigarette smoking, but do not appear to affect cognitive performance. These findings add to our understanding of the benefits and limitations of expectancy manipulations, both experimentally and as a treatment technique.

Abstract: There is a high degree of comorbidity between borderline personality disorder (BPD) and alcohol use disorders (AUDs). There is some evidence that this pattern of comorbidity may be associated with poorer prognosis. Although there are many different psychotherapeutic and pharmacological treatments for BPD and AUDs when they occur alone, there are very few treatment options when they occur together. The objective of this article was to review the existing treatment options-both psychotherapeutic and pharmacological-for patients with dual diagnoses of BPD and AUDs and to explore alternative treatment options that warrant further study. There have been a number of studies that have examined the efficacy of specific psychotherapies targeting drinking among patients with comorbid BPD; however, their efficacy in reducing BPD symptoms is unknown. There are also three psychotherapies that were specifically developed for patients with BPD and substance use disorders (SUDs), but only one of these (Dynamic Deconstructive Psychotherapy) has been tested among patients with dual diagnoses of BPD and AUDs. Research on pharmacotherapy for dual diagnoses of BPD and AUD is scarce, and no study has yet explored medication options that can concurrently manage symptoms of BPD and decrease alcohol consumption. Interestingly, there is growing evidence that anticonvulsants and second generation antipsychotics, the recent medications of choice for the management of BPD symptoms, may also reduce alcohol craving and consumption. Although premature, these findings are encouraging especially for this population of patients for whom treatment options are very limited.

Abstract: The dopamine D₃ receptor has received attention over the last two decades as a target for medications development for substance abuse disorders. Results have remained mixed. Despite emergence of more D₃-selective ligands, possible attribution of observed effects to D₂ receptors remains a concern. Knockout mice may help shed light on mechanisms. Here we evaluated the effect of constitutive D₃ receptor inactivation ("knockout") on the reinforcing effects of cocaine. We tested D₃ wild-type (WT), heterozygous (D₃⁺/⁻), and knockout (D₃⁻/⁻), mice in acquisition and maintenance of intravenous self-administration across a broad range of cocaine doses, using a fixed ratio (FR) 1 and a progressive ratio (PR) schedule of reinforcement, along with parallel food-reinforced studies. Generally, D₃⁻/⁻ mice showed cocaine self-administration comparable to WT controls across assays. Moderate and nonsignificant trends toward lesser reinforcing effects of a low cocaine dose (0.32 mg/kg) were apparent in acquisition and PR studies, consistent with the idea that the D₃ receptor may play a subtle role in the reinforcing effects of low cocaine doses under low FR conditions. However, those effects with cocaine self-administration were more subtle than the lower responding of D₃ knockout mice observed with food-maintained behavior. In addition, the D₃ antagonist PG01037 failed to affect cocaine self-administration under an FR 1 schedule in WT mice. The present data do not support a necessary role for the D₃ receptor in the direct reinforcing effects of cocaine.

Abstract: The purpose of the reported experiments was to examine the effects of imperatorin [9-(3-methylbut-2-enyloxy)-7H-furo[3,2-g]chromen-7-one], a bioactive furanocoumarin isolated from the fruits of Angelica archangelica (Angelica officinalis) on anxiety and memory-related behaviors of mice Male Swiss mice were tested for anxiety and cognition, in the elevated plus maze test (EPM), using two different procedures In the present experiments, imperatorin was administered acutely (at the doses of 5, 10, 20, 30, and 50 mg/kg); injections were made 15, 30, and 60 min before test (anxiety); 30 min before the first trial (memory acquisition); or immediately after the first trial (memory consolidation), as well as subchronically, twice a day for 6 days On the seventh day, the mice were injected once with imperatorin (10 and 20 mg/kg, ip) 30 min before the test (anxiety) and 30 min before the first trial (memory acquisition), or immediately after the first trial (memory consolidation) We observed that imperatorin when administered acutely and repeatedly, at the doses of 10 and 20 mg/kg, exerted an anxiolytic effect on mice tested 30 min after the injection measured in the EPM test By contrast, no such effect was observed after the acute administration of imperatorin at the doses of 5, 30 and 50 mg/kg Moreover, other observations carried out 15 and 60 min after a single injection of the drug did not reveal any effect of imperatorin on anxiety behavior in the EPM test Furthermore, acute and repeated administration of imperatorin (10 and 20 mg/kg) improved different stages of memory processes (both acquisition and consolidation) in a modified EPM test (mEPM) The results of our research suggest imperatorin to be an interesting therapeutical option in disorders with high anxiety levels and memory impairment

Abstract: A consistent observation in drug abuse research is that males and females show differences in their response to drugs of abuse. In order to understand the neurobiology underlying cocaine abuse and effective treatments, it is important to consider the role of sex differences. Sex hormones have been investigated in both behavioral and molecular studies, but further evidence addressing drug abuse and dependence in both sexes would expand our knowledge of sex differences in response to drugs of abuse. Neuroimaging is a powerful tool that can offer insight into the biological bases of these differences and meet the challenges of directly examining drug-induced changes in brain function. As such, neuroimaging has drawn much interest in recent years. Specifically, positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI) technology have emerged as effective noninvasive approaches for human and animal models. Studies have revealed sex-specific changes in patterns of brain activity in response to acute cocaine injection and after prolonged cocaine use. SPECT and PET studies have demonstrated changes in the dopamine transporter but are less clear on other components of the dopaminergic system. This review highlights contributions of neuroimaging toward understanding the role of sex differences in the drug abuse field, specifically regarding cocaine, and identifies relevant questions that neuroimaging can effectively address.

Abstract: Caffeinated alcoholic beverage (CAB) consumption is widespread among young adults in the United States and is associated with increased negative consequences from alcohol. In addition to the direct pharmacological effects of adding caffeine to alcohol, another possible risk mechanism is via socially learned expectancies, which has received very little consideration. The current study conducted an initial psychometric validation of a measure of CAB expectancies to facilitate research in this area. Participants were 409 undergraduate regular drinkers (71% female) who were assessed for alcohol and CAB use, alcohol use/misuse, and expectancies about CABs. The majority (62%) of participants reported CAB experience and 48% reported CAB use in the past month. Participants primarily consumed spontaneously-prepared as opposed to premixed-CABs. More frequent CAB use was significantly positively correlated with levels of alcohol use and misuse. For the expectancy items, exploratory factor analysis revealed two factors that were labeled "Intoxication Enhancement" and "Avoid Negative Consequences." The patterns of expectancies reflected beliefs that CABs enhanced intoxication, but did not protect against negative consequences. The measure was titled the Caffeine + Alcohol Combined Effects Questionnaire (CACEQ). Intoxication enhancement scores were significantly associated with frequency of CAB use, even after adjusting for the role of weekly drinking and alcohol misuse, supporting the convergent validity of the CACEQ. These data provide initial support for the CACEQ and suggest it may be useful for clarifying the role of expectancies in CAB use. Applications for studying the risks associated with CAB use and methodological considerations are discussed.

Abstract: The effects of chronic methamphetamine use on neuroendocrine functioning in humans are largely undocumented. Here we assessed basal plasma oxytocin, arginine vasopressin, and cortisol levels in a naturalistic sample of methamphetamine polydrug users (n = 12) compared with controls matched for age, gender, education, occupation status, and marital status (n = 17). All of the methamphetamine users tested positive for blood methamphetamine and/or its main metabolite, amphetamine. Other drugs of abuse were detected in a small number of methamphetamine users (MDMA [3,4-methylenedioxy-N-methylamphetamine; n = 2], THC [delta-9-tetrahydrocannabinol; n = 2]). Almost half of the methamphetamine users reported using methamphetamine intravenously, and others smoked or ingested the drug. Methamphetamine users had significantly lower basal plasma cortisol (p = .025), but similar basal plasma oxytocin and arginine vasopressin levels compared with controls. Basal plasma oxytocin was positively correlated (p = .011), with basal plasma arginine vasopressin in controls, but not in methamphetamine users. Methamphetamine users reported higher rates of psychiatric symptoms including substance use disorders, impulsivity, and positive, negative, manic, and disorientation symptoms compared with controls. Psychiatric symptoms were not related to neuroendocrine functioning in either group. These results provide preliminary evidence for lowered basal cortisol levels in methamphetamine polydrug users and encourage further research in to the effects of methamphetamine on neuroendocrine functioning in humans using more highly controlled experimental research designs.

Abstract: The association between smokers’ cue-induced craving and subsequent ability to initiate abstinence is unclear. Dependent smokers (N=158) completed a single cue-reactivity session prior to participating in a larger within-subjects study, which independently examined predictors of initiating quitting during 5 days each on nicotine versus placebo patch. In the larger study, all smokers used nicotine and placebo patch (double blind) for one week each following a preceding week of ad lib smoking, in a 2x2 cross-over design. Generalized estimating equation (GEE) models determined the predictive ability of cue-induced craving (cue reactivity) on subsequent success at initiating a quit attempt (at least 24hrs quit) for each patch condition. Smokers who exhibited greater craving during exposure to smoking cues had significantly greater odds of successfully initiating abstinence during either quit attempt week (i.e., the nicotine or placebo patch week). This relationship was not statistically significant for self-reported craving in response to neutral cues. However, a greater smoking-neutral cue difference score for cue-induced craving was also a significant predictor successfully initiating abstinence, but only among those not monetarily reinforced. Implications of these seemingly counterintuitive findings are discussed.

Abstract: A fundamental goal of double-blind alcohol challenge studies is to reduce alcohol expectancies, though there is little research on the effectiveness of blinding procedures and their relationship to acute alcohol responses. This study examined social drinkers' perception of beverage content and related alcohol response during 3 separate double-blind experimental sessions with placebo, low-dose alcohol (0.4 g/kg), and high-dose alcohol (0.8 g/kg). Using the alternative substance paradigm, participants (N = 182) were informed that the beverage they consumed might contain alcohol, a stimulant, a sedative, or a placebo. At several time points, subjective and objective measures were obtained, and participants were asked to identify which substance they received. During both placebo and low-dose alcohol sessions, 33% and 50% of participants, respectively, did not correctly identify the beverage content; during the high-dose alcohol session, 20% did not correctly identify the beverage. Although correct and incorrect identifiers at any dose level did not differ on major background variables, drinking characteristics, or psychomotor performance during these sessions, they did differ on self-reported subjective responses, with greater sedation reported by incorrect identifiers in the placebo and high-dose conditions. In summary, results suggest that the alternative substance paradigm may be a viable option for alcohol laboratory studies, particularly for repeated sessions in within-subject designs and in cases in which the experimenter wants to reduce expectancy by not revealing a priori that alcohol is being administered.

Abstract: Despite significant research demonstrating the deleterious effects of tobacco abstinence on memory, and research showing substantial sex differences in nicotine withdrawal and memory processes, there has been scant work on how males and females might differ in the effects of tobacco abstinence on memory and cognition. Using a standard recognition memory task, we conducted a pilot study to examine how 24 hours of tobacco abstinence in moderate to heavy smokers would affect memory in males and females. Twenty-five moderate to heavy smokers were tested following a period of smoking normally and following 24 hours of tobacco abstinence. At each session, participants completed a recognition memory task in which items were studied under full- and divided-attention conditions (a standard manipulation of memory encoding) as well as tests of passive short-term and working memory (forward and backward digit span). Tobacco abstinence significantly reduced memory performance under full attention conditions for males but not for females. A significant main effect of smoking status in which abstinence significantly reduced performance, as well as a main effect of encoding condition (divided attention < full attention), were found. Our results demonstrate that there may be substantial sex differences in the cognitive effects of tobacco abstinence. While preliminary, the data suggest the need for further, more extensive study of how males and females differ during tobacco abstinence. Such information will inform the best strategies for tobacco cessation efforts.

Abstract: The link between drinking motives and alcohol-related outcomes has been investigated extensively, yet almost exclusively using retrospective self-reports that are subject to recall bias. This study overcomes this limitation using an experimental design to test whether the 4 drinking-motive dimensions (social, enhancement, coping and conformity, as measured in the baseline questionnaire) predict the quantity of alcohol actually ingested during 2 wine-tasting sessions conducted approximately 3 and 7 weeks after the baseline motive assessment. Regression modeling was based on an analog measurement of grams of pure alcohol among 123 young adults. Self-reported data at baseline concurred with the data collected during the experimental sessions, that is, alcohol consumption was high for males and enhancement drinkers and low for conformity drinkers. Coping drinkers significantly increased their consumption between the first and second sessions, while social drinkers tended to decrease theirs. Yet when separately considering data recorded during the first session, none of the drinking motives predicted the amounts of alcohol actually consumed. To conclude, this study demonstrates that motives predict actual alcohol consumption, which is consistent with evidence-based self-reports. Particularly, enhancement and coping drinkers seem to take advantage of the drinking situation probably because they usually appreciate the psychoactive properties of alcohol, either to maximize pleasurable sensations or to alleviate negative ones. However, if the setting is unusual (first tasting session), situational characteristics may "overrule" the effect of personal motives. (PsycINFO Database Record (c) 2012 APA, all rights reserved). Language: en