ANXIOLYTIC AND ANTIDEPRESSANT MECHANISMS OF 5-HT1A 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 therap eutic effects in humans has resulted in considerable interest in the r ole of the 5-HT receptor system in both anxiety and depressive disorde rs. Because many of the clinically efficacious 5-HT1A anxiolytic drugs are either ineffective or produce inconsistent results in traditional or standard types of preclinical punishment or conflict procedures wi th rodents and other nonhuman mammals, there is considerable need for alternative behavioral assays sensitive to and selective for these com pounds. In contrast to data with nonhuman mammals, 5-HT1A drugs are qu ite effective in pigeons studied under a punishment procedure. This pa per reviews the use of the pigeon conflict procedure as a method for t he detection and analysis of potential anxiolytic drugs acting through 5-HT1A receptors. Additionally, recent studies, also with the pigeon, have indicated that, in contrast to the rat, it is possible to establ ish an antidepressant such as imipramine as a discriminative stimulus, and then to use this procedure to evaluate the neuropharmacological b ases for the behavioral and, presumably, therapeutic actions of these drugs. Using the drug discrimination procedure, it has been possible t o examine a number of selective compounds that substitute for imiprami ne, thereby clarifying specific substrates for the antidepressant acti vity of this and related drugs. The pigeon promises to be a useful spe cies in the pharmacological analyses of novel anxiolytic drugs and pro vides new approaches to the analysis and understanding of traditional as well as the more recently introduced antidepressant drugs.