Anxiolytic and antidepressant mechanisms of 5-HT_1A drugs in the pigeon: Contributions from behavioral studies

The discovery that compounds acting through 5-hydroxytryptamine (5-HT) receptor subtypes can produce anxiolytic and/or antidepressant therapeutic effects in humans has resulted in considerable interest in the role of the 5-HT receptor system in both anxiety and depressive disorders. Because many of the clinically efficacious 5-HT_1A anxiolytic drugs are either ineffective or produce inconsistent results in traditional or standard types of preclinical punishment or conflict procedures with rodents and other nonhuman mammals, there is considerable need for alternative behavioral assays sensitive to and selective for these compounds. In contrast to data with nonhuman mammals, 5-HT_1A drugs are quite effective in pigeons studied under a punishment procedure. This paper reviews the use of the pigeon conflict procedure as a method for the detection and analysis of potential anxiolytic drugs acting through 5-HT_1A receptors. Additionally, recent studies, also with the pigeon, have indicated that, in contrast to the rat, it is possible to establish an antidepressant such as imipramine as a discriminative stimulus, and then to use this procedure to evaluate the neuropharmacological bases for the behavioral and, presumably, therapeutic actions of these drugs. Using the drug discriination procedure, it has been possible to examine a number of selective compounds that substitute for imipramine, thereby clarifying specific substrates for the antidepressant activity of this and related drugs. The pigeon promises to be a useful species in the pharmacological analyses of novel anxiolytic drugs and provides new approaches to the analysis and understanding of traditional as well as the more recently introduced antidepressant drugs.