Pharmacological Models of Depression

The present paper reviews some currently used pharmacological models of depression. Pharmacological models of depression are those procedures which have been conceived with the aim of discovering antidepressants in experimental animals. The major criteria for the validity of such models are their sensitivity to known antidepressants (absence of false negatives) and their selectivity (absence of false positives). In addition pharmacological models of depression should be simple, rapid to perform and reliable. The present paper reviews models based on pharmacological interactions (reserpine, apomorphine, yohimbine, Clonidine) and those based on induced behavioural change (“behavioural despair”, tail suspension, “learned helplessness”, olfactory bulbectomy). All these models have a certain utility, apart from Clonidine where results are contradictory. Of the models based on a pharmacological interaction. yohimbine potent-iation in the mouse appears to have the greatest sensitivity and is very simple and rapid to perform. Of the behavioural models, “behavioural despair” has been subjected to the most intensive pharmacological validation and is both sensitive to a wide range of antidepressants and is simple and rapid to perform; false negatives include 5-HT uptake inhibitors and beta-adrenergic stimulants. Tail suspension is also simple and rapid but appears to be less sensitive; nonetheless 5-HT uptake inhibitors are active. “Learned helplessness” appears highly sensitive but is more time-consuming. Olfactory bulbectomy, although reasonably sensitive, is extremely time-consuming and of doubtful relevance to clinical depression.