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An autoradiographic study of the influence of pindolol upon [35S]GTPgammaS binding in rat, guinea pig and human brain

AuthorsSerrats, Jordi; Artigas, Francesc ; Mengod Los Arcos, Guadalupe ; Cortés, Roser
dorsal raphe
5-HT1A autoreceptors
Issue DateMar-2004
PublisherCambridge University Press
CitationInternational Journal of Neuro-Psychopharmacology 7 (1) : 27-34 (2004)
AbstractThe 5-HT1A/beta-adrenoceptor ligand (+/-)pindolol has been used in clinical trials to enhance the antidepressant effect of selective serotonin (5-HT) reuptake inhibitors (SSRIs). The accelerating effect of (+/-)pindolol is thought to derive from its blockade of the SSRI-induced, 5-HT1A autoreceptor-mediated inhibition of serotonergic cell firing and 5-HT release. However, controversial results have been reported in regard to its ability to antagonize the effect of 5-HT at such receptors. In the present study, we have analysed the effect of (+/-)pindolol on receptor-mediated G-protein activation by measuring guanylyl 5'-[gamma-[35S]thio]-triphosphate ([35S]GTPgammaS) binding onto tissue sections from the hippocampus and dorsal raphe nucleus from rat, guinea pig and human brain. In these regions, enriched in 5-HT1A receptors, (+/-)pindolol antagonized the stimulation of [35S]GTPgammaS binding induced by 5-HT in a concentration-dependent manner. We found that in both rat and human brain the calculated pEC50 values were higher in the dorsal raphe nucleus than in hippocampus. This suggests a higher potency of (+/-)pindolol at somatodendritic 5-HT1A receptors compared to post-synaptic 5-HT1A sites. In the absence of 5-HT, (+/-)pindolol (up to 10(-3) M) did not modify [35S]GTPgammaS binding, which remained at basal levels, indicating that, in this assay, (+/-)pindolol acts as a neutral antagonist rather than a partial agonist as it has been observed in other experimental models. The present data are relevant for the understanding of the neurobiological basis of pindolol acceleration of the action of SSRI antidepressants.
Publisher version (URL)http://journals.cambridge.org/download.php?file=/PNP/PNP7_01/S1461145703003924a.pdf&code=a7e5431b44cb3f0a00828a47df480146
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