Models for depression

Antidepressant Drugs. Figure 1 Effects of stress as a model for depression and the reversal by the use of antidepressants. Multiple intracellular targets might be involved in the regulation of plasticity and resilience by antidepressants, which block extracellular transporters. Adapted from [1],... 

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...

Animal behavioral models can be used to evaluate the effect of antidepressants on depression [Thiebot et al. 1992]. If TMS and ECT exert antidepressant effects by a similar mechanism, animal models for depression that are sensitive to electroconvulsive shock [ECS] should also be sensitive to TMS. ECS has effects on known animal models for depression. These effects may be displayed after recovery from the immediate effects of the convulsions [Thiebot et al. 1992]. We evaluated the effects of TMS on the forced swimming test and on apomorphine-induced stereotypy, a sensitive behavioral measure for the effects of repeated ECS. 

Repeated ECS enhances apomorphine and other dopamine agonist-induced hyperactivity and stereotypy [Grahame-Smith et al. 1978 A. R. Green 1984 Modigh 1989]. Although apomorphine-stimulated behavior is not a face valid model for depression, ECS sensitizes apomorphine-stimulated behavior very... 

The above project represents a novel approach and a possible new treatment for psychiatric disorder. The possibility that neuronal discharge short of total brain convulsion may have psychiatric effects would be a major advance in understanding the action of ECT. Moreover, a possible substitute treatment for ECT would be a major clinical breakthrough. TMS might allow us to stimulate deep brain regions without convulsions, pain, or known hazards. Before one widens the use of TMS in humans, further evaluation of the effectiveness of TMS in animal models for depression is necessary. Our hypothesis is that ECT exerts its therapeutic effects by stimulation of specific brain regions. We suggest that TMS may exert therapeutic effects without need for total brain convulsion. 

As examples for the wide field of specific disease areas and mouse models, we have included type 1 and 2 diabetes (Serreze and Baribault), cardiovascular disease (Howies), arthritis (Tak), skin disorders (Sundberg), cancer (Talmadge, Surguladze, and Li), the use of behavioral models for depression and anxiety (Kalueff), neurodegenerative diseases (Janus), neuromuscular diseases (Burgess), and infectious diseases (Medina). 

New Screening Methods - New animal models for depression Included the... 

The early finding that chronic treatment of rats with buspirone induced a down-regulation of central S-HTj receptors initiated the extensive testing of S-HTj receptor ligands, such as buspirone, gepirone, ipsapirone and 8-OH-DPAT, in animal models for depression. All these compounds displayed anti-depressive... 

Procedures that have been suggested as models of depression and used to look for neurochemical changes that parallel the onset of the behavioural change, as well as to test how antidepressants affect the behaviour, are listed in Table 20.3. Those that have been used most, either as a drug screen or in research into the neurobiology of depression, are as follows. 

Long-term potentiation and depression of glutamatergic synapses are involved in many models for brain function and development. A key factor in the plasticity is a change in the AMPA and kainate... 

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. 

Uncertainty factors Interspecies 3—The monkey was more susceptible than the rat the lowest concentration in a range was chosen (70 ppm) humans and monkeys showed changes in the visual evoked response at similar concentrations the monkey is a good model for the human. The concentration inducing central nervous system depression does not vary greatly among mammalian species. Intraspecies 3—Individual variation in susceptibility to central nervous system depressants such as anesthetics varies no more than 2-fold. 

Mannucd C, Tedesco M, BeUomo M, Caputi AP, Calapai G (2006) Long-term effects of nicotine on the forced swimming test in mice an experimental model for the study of depression caused by smoke. Neurochem Int 49 481 86... 

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