Depression animal models

Key words Depression, animal models, antidepressant drug screening, despair, anhedonia, chronic stress. 

Newport DJ, Stowe ZN, Nemeroff CB. Parental depression animal models of an adverse life event. Am. J. Psychiatry 2002 159 1265-1283. 

Developing an animal model of bipolar disorder is challenging, due to the dramatically different clinical presentations of mania and depression. Animal models of depression are described above, and can be considered to model the depres-... 

They act as analgesics by inhibiting release of nociceptive neurotransmitters from primary afferent terminals as well as by depressing post-synaptic potentials on second order neurons. Opioid receptors are also present on some nociceptors and their expression and peripheral transport is increased upon peripheral inflammation. Peripheral opioid analgesia has been established in animal models. Although clinical studies have yielded mixed results so far, this field holds great promise. Despite side effects, such as euphoria, dysphoria, sedation, respiratory depression and obstipation and tolerance and dependence phenomena which arise upon... 

Relcovaptan (SR-49059) is a selective, orally active V1aR antagonist that prevents pain of primary dysmenorrhea and inhibits preterm labour and could be useful in the treatment of Raynaud s phenomenon. The selective ViBR antagonist SSR149415 showed beneficial effects in the treatment of depression and anxiety in several animal models. 

Specific animal models are discussed in some detail in the appropriate chapters on epilepsy, depression, schizophrenia, etc. 

Attempts to find the cause(s) of depression have adopted two main approaches. One is to look for the neurobiological basis of depression in human subjects and animal models of this condition. The second is to investigate the pharmacology of established antidepressant agents to see whether they consistently augment some, and ideally the same, neurobiological targets in the brain. 

The use of animal models for depression has two main objectives. One is to provide a behavioural model that can be used to screen potential antidepressant treatments. For this, the behaviour does not have to be an animal analogue of depression all that is needed is for it to be consistently prevented by established antidepressant agents (i.e. no false negatives) but not by drugs which have no antidepressant effect in humans (i.e. no false positives). 

Table 20.3 Procedures that have been used as animal models for depression or as a preclinical...

Willner, P (1984) The validity of animal models of depression. Psychopharmacology 83 1-16. 

Leonard BE (1985). Animal models of depression and the detection of antidepressants. In SD Iversen (ed.), Psychopharmacology Recent Advances and Future Prospects (pp. 33—43). Oxford University Press, Oxford, UK. 

Weiss, I. M. and Simson, P. E. Neurochemical and electro-physiological events underlying stress-induced depression in an animal model Adv. Exp. Med. Biol. 245 425-440, 1988. 

There are three generally accepted criteria for validating animal models for human psychiatric disorders face validity, construct validity, and predictive validity. Face validity refers to the outward appearance of the model, i.e. does the animal s behavior adequately reflect the human behavior being modeled In this dimension, anxiety models have a clear advantage over other psychiatric models it is usually quite apparent if an animal is frightened, whereas it is a much more difficult to assess whether an animal is displaying psychotic-like or depressive-like behavior, for example. 

Compound SR 95191 (42, CAS 94011-82-2) is another aminopyridazine-derived antidepressant agent structurally closely related to minaprine, which has been investigated in France quite recently [ 160-162], This compound has been shown to be active in most animal models of depression with an activity profile resembling that of a selective type A MAO inhibitor [ 160], Recently, it has been found that this inhibition is selective, reversible and competitive in vivo in vitro, however, SR 95191 behaves like an irreversible MAO-A inhibitor [162],... 

However, the use of CAP was soon restricted after its association with bone marrow depression and aplastic anemia. The underlying biochemical lesion is still obscure, and adequate animal models are lacking. Since thiamphenicol, a CAP analogue where the nitro function has been replaced by a MeSC>2 -group, has never been associated with aplastic anemia, Yunis and coworkers suggested that the p-n il.ro group of CAP may be involved in the development of aplastic anemia129,130. 

AS 1990). Several 5-HTlA agonists have been found to produce anxiolytic effects in animal models and in human clinical trials (File et al. 1996 Krummel and Kathol 1987 Goldberg and Finnerty 1979). Furthermore, they have antidepressant effects they augment the antidepressant effects of serotonin reuptake inhibitors, and they decrease the therapeutic latency (Bouwer and Stein 1997 Artigas et al. 1996 Sussman 1998 Rickels et al. 1991 Wieland and Lucki 1990 Jenkins et al. 1990 Fabre 1990). However, results have not been uniformly positive, such as in refractory severe depression (Sussman 1998 Fischer et al. 1998)... 

Recent in vitro hybridization studies in the rat have demonstrated that t)rpical antidepressants increase the density of glucocorticoid receptors. Such an effect could increase the negative feedback mechanism and thereby reduce the s)mthesis and release of cortisol. In support of this hypothesis, there is preliminary clinical evidence that metyrapone (and the steroid s)mthesis inhibitor ketoconazole) may have antidepressant effects. Recently several lipophilic antagonists of corticotrophin releasing factor (CRT) type 1 receptor, which appears to be hyperactive in the brain of depressed patients, have been shown to be active in animal models of depression. Clearly this is a potentially important area for antidepressant development. 

Whishaw IQ, Metz GA, Kolb B, Pellis SM (2001) Accelerated nervons system development contributes to behavioral efficiency in the laboratory mouse a behavioral review and theoretical proposal. Dev Psychobiol 39 151-170 Willner P (1984) The validity of animal models of depression. Psychopharmacology (fieri)... 

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