Depression antidepressant drug testing

In the learned helpless model, animals (usually rats) are subjected to a brief (l-2h) inescapable shock. Subsequently, they are tested in a task in w hich they can terminate the shock by an operant response. Animals w ith prior inescapable shock exposure do not perform as w ell in the test (Maier and Watkins, 2005). Advantages of the learned helplessness model include its use in studies of neurochemical changes, and that it responds to repeated, rather than acute, antidepressant drug adminish ation. Disadvantages of the model include its dependence on acute stress adminish ation, suggesting it may better model posthau-madc stress disorder than major depressive disorder. 

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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. 

There was a problem with this first version of the biochemical theory of depression. Iproniazid was not the only drug that had been reported to be effective as an antidepressant. Imipramine, the drug that had been tested by the Swiss psychiatrist Roland Kuhn, seemed to have similar effects. But imipramine is not an MAOI it does not inhibit the destruction of neurotransmitters in the synapse. So if antidepressants worked by inhibiting monoamine oxidase, why was imipramine effective How could its apparent effectiveness be reconciled with the chemical-imbalance theory ... 

In the late 1950s, imipramine was noted to be effective for the symptomatic treatment of depression. A number of chemical congeners of imipramine have been synthesized and tested for antidepressant properties they are collectively known as TCAs. The TCAs are no longer considered first-line agents in the treatment of depression because of their prominent side effects and the need to monitor drug blood levels to avoid toxicity. 

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