Modification of 5‐HT neuron properties by sustained administration of the 5‐HT 1A agonist gepirone: Electrophysiological studies in the rat brain

Modification of 5‐HT neuron properties by sustained administration of the 5‐HT 1A agonist... The sustained administration of the 5‐HT1A 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‐HT1A receptor by gepirone, should result in an augmented tonic activation of postsynaptic 5‐HT1A receptors. The progressive appearance of this phenomenon would be consistent with the time course of the clinical anxiolytic, and possibly antidepressant, effects of gepirone. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Synapse Wiley

Modification of 5‐HT neuron properties by sustained administration of the 5‐HT 1A agonist gepirone: Electrophysiological studies in the rat brain

Synapse, Volume 1 (5) – Jan 1, 1987

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Publisher
Wiley
Copyright
Copyright © 1987 Alan R. Liss, Inc.
ISSN
0887-4476
eISSN
1098-2396
DOI
10.1002/syn.890010511
pmid
2905533
Publisher site
See Article on Publisher Site

Abstract

The sustained administration of the 5‐HT1A 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‐HT1A receptor by gepirone, should result in an augmented tonic activation of postsynaptic 5‐HT1A receptors. The progressive appearance of this phenomenon would be consistent with the time course of the clinical anxiolytic, and possibly antidepressant, effects of gepirone.

Journal

SynapseWiley

Published: Jan 1, 1987

References

  • Effects of the two antidepressant drugs mianserin and indalpine on the serotonergic system: Single‐cell studies in the rat
    Blier, Blier; de Montigny, de Montigny; Tardif, Tardif
  • Short‐term lithium treatment enhances responsiveness of postsynaptic 5‐HT 1A receptors without altering 5‐HT autoreceptor sensitivity: An electrophysiological study in the rat brain
    Blier, Blier; de Montigny, de Montigny; Tardif, Tardif
  • Electrophysiology of hippocampal neurons. II. After‐potentials and repetitive firing
    Kandel, Kandel; Spencer, Spencer
  • Electrophysiological responses of serotoninergic dorsal raphe neurons to 5‐HT 1A and 5‐HT 1B agonists
    Sprouse, Sprouse; Aghajanian, Aghajanian

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