Region-specific changes in 5-HT 1A receptor-activated G-proteins in rat brain following chronic buspirone

Region-specific changes in 5-HT 1A receptor-activated G-proteins in rat brain following chronic... 5-Hydroxytryptamine 1A (5-HT 1A ) receptors, which activate inhibitory G-proteins, are implicated in psychiatric disorders including anxiety and depression. Studies suggest that chronic 5-HT 1A receptor agonist administration alters 5-HT 1A receptor function, but the effect of chronic treatment on 5-HT 1A receptor-activated G-proteins is unclear. In this study, agonist-stimulated ( 35 S)guanylyl-5′- O -(γ-thio)-triphosphate (GTPγS) binding was examined following chronic administration of buspirone. Brains were processed for ( 35 S)GTPγS autoradiography using R (+)-8-hydroxy-2-(di- n -propylamino)tetralin (8-OH-DPAT) for 5-HT 1A receptors or baclofen for GABA B receptors. Net 8-OH-DPAT-stimulated ( 35 S)GTPγS binding was decreased by 25–30% in the septum and dorsal raphe nucleus of buspirone-treated animals. No significant changes in 8-OH-DPAT-stimulated ( 35 S)GTPγS binding were found in the prefrontal, entorhinal or cingulate cortices or hippocampus in buspirone-treated rats. GABA B receptor-stimulated ( 35 S)GTPγS binding was increased by 25% in the hippocampus, with no significant changes in any other region examined. These results demonstrate region-specific alterations in 5-HT 1A and GABA B receptor-activated G-proteins following chronic buspirone treatment, which may contribute to the clinical effects of this drug. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Pharmacology Elsevier

Region-specific changes in 5-HT 1A receptor-activated G-proteins in rat brain following chronic buspirone

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Publisher
Elsevier
Copyright
Copyright © 2000 Elsevier Science B.V.
ISSN
0014-2999
DOI
10.1016/S0014-2999(99)00875-4
Publisher site
See Article on Publisher Site

Abstract

5-Hydroxytryptamine 1A (5-HT 1A ) receptors, which activate inhibitory G-proteins, are implicated in psychiatric disorders including anxiety and depression. Studies suggest that chronic 5-HT 1A receptor agonist administration alters 5-HT 1A receptor function, but the effect of chronic treatment on 5-HT 1A receptor-activated G-proteins is unclear. In this study, agonist-stimulated ( 35 S)guanylyl-5′- O -(γ-thio)-triphosphate (GTPγS) binding was examined following chronic administration of buspirone. Brains were processed for ( 35 S)GTPγS autoradiography using R (+)-8-hydroxy-2-(di- n -propylamino)tetralin (8-OH-DPAT) for 5-HT 1A receptors or baclofen for GABA B receptors. Net 8-OH-DPAT-stimulated ( 35 S)GTPγS binding was decreased by 25–30% in the septum and dorsal raphe nucleus of buspirone-treated animals. No significant changes in 8-OH-DPAT-stimulated ( 35 S)GTPγS binding were found in the prefrontal, entorhinal or cingulate cortices or hippocampus in buspirone-treated rats. GABA B receptor-stimulated ( 35 S)GTPγS binding was increased by 25% in the hippocampus, with no significant changes in any other region examined. These results demonstrate region-specific alterations in 5-HT 1A and GABA B receptor-activated G-proteins following chronic buspirone treatment, which may contribute to the clinical effects of this drug.

Journal

European Journal of PharmacologyElsevier

Published: Feb 18, 2000

References

  • Effects of propranolol, buspirone, pCPA, reserpine and chlordiazepoxide on open-field behavior
    Angrini, M.; Leslie, J.C.; Shephard, R.A.
  • Modification of 5-HT neuron properties by sustained administration of the 5-HT 1A agonist gepirone: electrophysiological studies in the rat brain
    Blier, P.; De Montigny, C.
  • Blockade of the antidepressant-like effects of 8-OH-DPAT, buspirone and desipramine in the rat forced swim test by 5HT 1A receptor antagonists
    Detke, M.J.; Weiland, S.; Lucki, I.
  • Efficacy of buspirone in alcohol dependence: a review
    Malec, T.S.; Malec, E.A.; Dongier, M.
  • Involvement of GABA B receptor systems in action of antidepressants: baclofen but not bicuculline attenuates the effects of antidepressants on the forced swim test in rats
    Nakagawa, Y.; Ishima, T.; Ishibashi, Y.; Yoshii, T.; Takashima, T.
  • A comparison of the effects of 8-OH-DPAT pretreatment on different behavioural responses to 8-OH-DPAT
    O'Connell, M.T.; Curzon, G.

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