The olfactory bulbectomised rat as a model of depression

The ability to modify mice genetically has been one of the major breakthroughs in modern medical science affecting every discipline including psychiatry. It is hoped that the application of such technologies will result in the identification of novel targets for the treatment of diseases such as depression and to gain a better understanding of the molecular pathophysiological mechanisms that are regulated by current clinically effective antidepressant medications. The advent of these tools has resulted in the need to adopt, refine and develop mouse-specific models for analyses of depression-like behavior or behavioral patterns modulated by antidepressants. In this review, we will focus on the utility of current models (eg forced swim test, tail suspension test, olfactory bulbectomy, learned helplessness, chronic mild stress, drug-withdrawal-induced anhedonia) and research strategies aimed at investigating novel targets relevant to depression in the mouse. We will focus on key questions that are considered relevant for examining the utility of such models. Further, we describe other avenues of research that may give clues as to whether indeed a genetically modified animal has alterations relevant to clinical depression. We suggest that it is prudent and most appropriate to use convergent tests that draw on different antidepressant-related endophenotypes, and complimentary physiological analyses in order to provide a program of information concerning whether a given phenotype is functionally relevant to depression-related pathology.

In search of a depressed mouse: utility of models for studying depression-related behavior in genetically modified mice.

Here, we characterized behavioral abnormalities induced by prolonged social isolation in adult rodents. Social isolation induced both anxiety- and anhedonia-like symptoms and decreased cAMP response element–binding protein (CREB) activity in the nucleus accumbens shell (NAcSh). All of these abnormalities were reversed by chronic, but not acute, antidepressant treatment. However, although the anxiety phenotype and its reversal by antidepressant treatment were CREB-dependent, the anhedonia-like symptoms were not mediated by CREB in NAcSh. We found that decreased CREB activity in NAcSh correlated with increased expression of certain K 1 channels and reduced electrical excitability of NAcSh neurons, which was sufficient to induce anxietylike behaviors and was reversed by chronic antidepressant treatment. Together, our results describe a model that distinguishes anxiety- and depression-like behavioral phenotypes, establish a selective role of decreased CREB activity in NAcSh in anxiety-like behavior, and provide a mechanism by which antidepressant treatment alleviates anxiety symptoms after social isolation. Depression and anxiety are common forms of mental illness in the general population. Although they are classified as distinct syndromes by the Diagnostic and Statistical Manual (American Psychiatric Association), symptoms of depression and anxiety often occur together and to widely varying extents in different subtypes of the illnesses. Despite the importance of these clinical phenomena, very little is known about the distinctions between depression- and anxiety-like symptoms in animal models 1 . Models of ‘active’ stress, such as foot shock, restraint stress, social defeat and learned helplessness, produce depressionand anxiety-like phenotypes; the molecular mechanisms of these models have been extensively studied, but specific molecular mediators of depression versus anxiety symptoms have not yet been described 2‐4 . Even less well studied, however, is a ‘passive’ model of stress and social isolation in adulthood, which, as with active stress, mimics aspects of human depression and anxiety 5,6 . This lack of attention is unfortunate, as social isolation would appear to be particularly relevant to certain subtypes of human depression and anxiety disorders 7,8 . Although social isolation has been studied, most models to date have focused on adulthood behaviors after isolation rearing early in life, either as pups or adolescents, which is a very different model than adulthood social isolation 5 . Reports on adulthood isolation provide

http://basicmed.med.ncku.edu.tw/admin/up_img/980522-2.pdf

CREB regulation of nucleus accumbens excitability mediates social isolation-induced behavioral deficits

The amygdala has been attributed with a considerable number of very diverse functions. Its involvement in learning and memory, though, has found increased attention. Following a short description of the connections of the amygdala and its critical neurotransmitters, studies are reviewed here in which the amygdala's activity was manipulated or observed by different methods (lesions, electrical brain stimulation, neurochemical intra-amygdaloid injections, single-unit recordings). Some of the major conclusions resulting from this data analysis indicate an advantage in performing subtotal amygdaloid lesions over an amygdalectomy, a point of view that is especially supported by the heterogeneous anatomical connections of different amygdaloid nuclei. Thereafter, an evaluation is made of different tasks with respect to their discriminative sensitivity to amygdaloid manipulations. Some species-specific differences in performing certain tasks after amygdaloid injuries are discussed in relation to the different expansion of amygdalo-cortical connections in higher and less highly encephalized species. Finally, some general assumptions are made on the specific role of each of the amygdaloid nuclei during the mnemonic processes attributed to the amygdala. It is concluded that emotionally significant information is encoded and can be retrieved on the basis of the structures and connections of the basolateral limbic circuit.

Involvement of the amygdala in learning and memory: a critical review, with emphasis on anatomical relations.

Sensory Evolution on the ThresholdAdaptations in Secondarily Aquatic Vertebrates

Differential effects of peripheral and central anosmia producing techniques on spontaneous behavior patterns.

Olfactory perception and bulbar electrical activity in several avian species

The role of the olfactory system in avoidance learning and activity.

Selective olfactory bulb lesions: Reactivity changes and avoidance learning in rats

Electrical activity of the olfactory bulb of the pigeon.

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