The overall objective of this proposal is to study how the different types of 5-hydroxytryptamine (5-HT) receptors that have been identified recently by ligand binding techniques regulate discrete behavioral functions which are important to the mechanism of action of antidepressant and antianxiery medications. Chronic administration of different types of antidepressant drugs alter the density of 5-HT receptors. In addition, new anxiolytic drugs, such as buspirone, have been suggested to produce anxiolytic and/or antidepressant effects by pharmacological actions ar the 5-HIlA receptor. The purpose of this proposal is to use animal behavior models associated with the activation of selective types of 5-HT receptors to study pharmacological actions that are important to the therapeutic effects of antidepressant and anxiolytic drugs. Although we have studied unconditioned behaviors elicited by 5-HT agonists as model of 5-HT receptor activation, the present studies will also use conditioned behaviors because they may provide information useful for understanding how humans experience drug effects. Animal are trained to discriminate selective 5-HT agonists and to distinguish the internal state produced by these drugs from drugs with other effects. Since changes in 5-HT 1A and 5-HT2 receptors have been proposed to mediate the effects of antidepressant and anxiolytic drugs will will study discrimination of the 5-HT 1A agonist DPAT and the 5-HT agonist DOB as behavioral models for measuring functional alterations of 5-HT receptor that may be involved in therapeutic effects of these drugs. We will also use information obtained in the above experiments to study the anticonflict effects of 5-HT 1A-selective anxiolytics and to exmaine the involvement of 5-HT receptors in their anxiolytic effects.
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