Endogenous opiates and behavior: 2009.

The non-medical use of prescription opiates, such as Vicodin® and MSContin®, has increased dramatically over the past decade. Of particular concern is the rising popularity of these drugs in adolescent female populations. Use during this critical developmental period could have significant long-term consequences for both the female user as well as potential effects on her future offspring. To address this issue, we have begun modeling adolescent opiate exposure in female rats and have observed significant transgenerational effects despite the fact that all drugs are withdrawn several weeks prior to pregnancy. The purpose of the current set of studies was to determine whether adolescent morphine exposure modifies postpartum care. In addition, we also examined juvenile play behavior in both male and female offspring. The choice of the social play paradigm was based on previous findings demonstrating effects of both postpartum care and opioid activity on play behavior. The findings revealed subtle modifications in the maternal behavior of adolescent morphine-exposed females, primarily related to the amount of time females’ spend nursing and in non-nursing contact with their young. In addition, male offspring of adolescent morphine-exposed mothers (MOR-F1) demonstrate decreased rough and tumble play behaviors, with no significant differences in general social behaviors (i.e. social grooming and social exploration). Moreover, there was a tendency toward increased rough and tumble play in MOR-F1 females, demonstrating the sex-specific nature of these effects. Given the importance of the postpartum environment on neurodevelopment, it is possible that modifications in maternal-offspring interactions, related to a history of adolescent opiate exposure, plays a role in the observed transgenerational effects. Overall, these studies indicate that the long-term consequences of adolescent opiate exposure can impact both the female and her future offspring.

/pdf/adolescent-opiate-exposure-in-the-female-rat-induces-subtle-248728veps.pdf

Adolescent Opiate Exposure in the Female Rat Induces Subtle Alterations in Maternal Care and Transgenerational Effects on Play Behavior

Studies have intimated a role for endogenous opioids in skeletal ontogeny. We hypothesized that this role may be confined to the perinatal period. We, therefore, examined both fetal and postnatal rat long bones to determine the pattern, if any, of mu receptor expression. Perfused long bones and brains were harvested from 3 to 4 each of near-term fetuses, 3- to 4-week-old neonates, and 6-week-old juveniles. Tissues were decalcified, embedded, sectioned, quenched of peroxidase, and then blocked. Sections were incubated overnight with either rabbit antirat mu receptor IgG or naive rabbit IgG (control) at 4 degrees C. The next day, sections were washed, blocked again, and incubated with biotin-labeled secondary antibody, streptavidin-peroxidase conjugate, and a chromogen substrate with intervening wash steps. Slides were counterstained with hematoxylin and coverslipped. Digital photomicrographs were then imported into an image analysis program and the percent area of stained cortical and trabecular bone quantified. Mu receptor expression decreased significantly with age. Approximately 25% of the area of fetal long bones stained positively, including the endosteum, periosteum, and the growth plate. Little or no nonspecific staining occurred. Staining in neonatal tissue was diminished to <11% of the area and involved areas of apparent remodeling; chondrocytes in the growth plates failed to stain. Finally, juvenile bone evidenced staining approaching background levels produced by control slides (approximately 2%). Mu receptors are abundant in developing rat long bones during fetal development but become progressively less abundant postnatally. This infers a role for endogenous opioids during skeletal ontogeny.

Fate of mu receptors during rat skeletogenesis.

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Fate of mu receptors during rat skeletogenesis.