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. © 1992 Wiley‐Liss, Inc.
Drug Development Research – Wiley
Published: Jan 1, 1992
Keywords: serotonin 5‐HT 1A receptor; antidepressant; pigeon
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