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.
European Journal of Pharmacology – Elsevier
Published: Feb 18, 2000
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