STUDIES ON THE EFFECTS OF 5-HT(1A) DRUGS IN THE PIGEON

A number of compounds with high receptor binding affinity for the 5-hydroxytryptamine (5-HT) receptor subtype designated as 5-HT1A Can produce anxiolytic and/or antidepressant effects in humans. In contrast to the traditional benzodiazepine anxiolytics, many of the clinically efficacious 5-HT1A drugs are either ineffective or produce inconsistent results in traditional preclinical anxiolytic screens using behavioral procedures with rodents. In preclinical antidepressant models with these animals, however, effects of the 5-HT1A drugs, as well as those of traditional antidepressant compounds, are predictive of their antidepressant activity in humans. In contrast, 5-HT1A drugs are quite effective in pigeons studied under a rather conventional punishment or conflict-type procedure that is also sensitive to the benzodiazepine anxiolytics. However, traditional antidepressant compounds, such as the tricyclic drugs amitriptyline and imipramine, as well as the 5-HT reuptake blockers such as fluoxetine, do not show effects similar to the newer 5-HT1A drugs in this procedure. Thus, in rodents, current antidepressant models are sensitive to drugs that appear to function through different mechanisms, whereas conflict-type procedures typically do not reveal anxiolytic-like effects with 5-HT1A drugs. The pigeon conflict procedure, however, discriminates between the 5-HT1A antidepressants and antidepressant drugs functioning through other systems, whereas the effects of known anxiolytics in this procedure are quite similar. Increases in punished responding with 5-HT1A drugs correlates highly (r= +0.83) with affinity for the 5-HT1A receptor in pigeons. This paper reviews behavioral studies conducted with the pigeon in which the focus has been on the analysis of 5-HT1A compounds and addresses additional work that is required to answer many of the outstanding questions about this new class of anxiolytic and/or antidepressant drugs.