Modification of 5‐HT neuron properties by sustained administration of the 5‐HT1A agonist gepirone: Electrophysiological studies in the rat brain
Synapse – January 01, 1987
Source: OpenAlex
Summary
Sustained administration of the 5-HT1A agonist gepirone (15 mg/kg/day) in rats led to a significant initial drop in dorsal raphe serotonin neuron activity, which normalized after 14 days. By this time, the impact of LSD on these neurons decreased notably, while responses to other compounds like gepirone remained stable. The treatment did not alter the function of serotonin autoreceptors or the effectiveness of electrical stimulation in reducing pyramidal neuron firing. This suggests potential enhanced postsynaptic receptor activation, aligning with gepirone's anxiolytic and antidepressant effects.
Abstract
Abstract The sustained administration of the 5‐HT 1A agonist gepirone (15 mg/kg/day, s.c.) in the rat produced an initial decrease of the firing activity of dorsal raphe 5‐HT neurons which was followed by a progressive recovery to normal after 14 days of treatment. At this point in time, the effect of intravenous lysergic acid diethylamide (LSD) on the firing activity of 5‐HT neurons was markedly reduced, whereas those of 8‐hydroxy‐2‐N, N‐propylamino‐tetralin (8‐OH‐DPAT) and of gepirone were unchanged; however, the responsiveness of 5‐HT neurons to direct microintophoretic application of 5‐HT, LSD, 8‐OH‐DPAT, and gepirone, but not of GABA, was reduced. The responsiveness of postsynaptic dorsal hippocampus pyramidal neurons to 5‐HT, 8‐OH‐DPAT, and gepirone was not altered by the 14‐day gepirone treatment. The effectiveness of the electrical stimulation of the ascending 5‐HT pathway in reducing pyramidal neuron firing activity was not significantly modified in rats treated with gepirone for 14 days. Furthermore, this treatment did not alter the function of the terminal 5‐HT autoreceptor. It is concluded that the progressive restoration of the firing activity of 5‐HT neurons, due to a desensitization of the somatodendritic 5‐HT autoreceptor, combined with the direct activation of normosensitive postsynaptic 5‐HT 1A receptor by gepirone, should result in an augmented tonic activation of postsynaptic 5‐HT 1A receptors. The progressive appearance of this phenomenon would be consistent with the time course of the clinical anxiolytic, and possibly antidepressant, effects of gepirone.