Modification of 5‐HT neuron properties by sustained administration of the 5‐HT1A agonist gepirone: Electrophysiological studies in the rat brain
Synapse January 1, 1987 Pierre Blier, Claude de Montigny 428 citations
Rats given the 5-HT1A agonist gepirone for 14 days initially showed reduced firing of serotonin neurons in the dorsal raphe, which gradually returned to normal. After 14 days, the response of these neurons to intravenous LSD was markedly reduced, while responses to 8-OH-DPAT and gepirone were unchanged. Direct application of serotonin, LSD, 8-OH-DPAT, and gepirone to the neurons showed reduced responsiveness, but not to GABA. Postsynaptic hippocampal neurons remained normally responsive to serotonin and related drugs. The findings suggest that desensitization of somatodendritic 5-HT autoreceptors, combined with normal postsynaptic receptor activation, leads to increased tonic activation of postsynaptic 5-HT1A receptors, consistent with the delayed clinical anxiolytic and antidepressant effects of gepirone.