Adaptive changes in the serotonergic system are generally believed to underlie the therapeutic effectiveness of the azapirone anxiolytics and a variety of antidepressant drugs. The serotonin-1A (5-HT(1A)) receptor has been implicated in affective disorders. Thus, studies of the regulation of 5-HT(1A) receptor function may have important implications for our understanding the role of this receptor in the mechanism of action of these therapeutic agents. This review focuses on the regulation of central 5-HT(1A) receptor function following administration of 5-HT(1A) receptor agonists or antidepressant drugs expected to increase the synaptic concentration of the neurotransmitter 5-HT. The majority of evidence supports regional differences in the regulation of central 5-HT(1A) receptor function following repeated agonist or antidepressant administration, which may be due to differences in processes involved in desensitization of the receptor at the cellular level. Region-specific differences in the regulation of 5-HT(1A) receptor function may be based on compensatory changes distal to the receptor, such as regulatory changes at the level of effector (e.g. adenylyl cyclase or ion channel), or at the level of the G protein such as changes in G protein expression, or phosphorylation of the G protein. It may be that the increase in serotonin neurotransmission, due to somatodendritic autoreceptor desensitization following agonist or antidepressant treatment, to normo-sensitive 5-HT(1A) receptors in certain brain regions (e.g. hippocampus or cortex) and to sub-sensitive 5-HT(1A) receptors in other brain regions (e.g. amygdala or hypothalamus) underlies the therapeutic efficacy of these drugs.
Copyright 2002 Elsevier Science Inc.