Pindolol antagonises G-protein activation at both pre- and postsynaptic serotonin 5-HT1A receptors: a [S-35]GTP gamma S autoradiography study

The arylalkylamine, pindolol, may potentiate the clinical actions of antide pressant agents. Although it is thought to act via blockade of 5-HT1A autor eceptors, its efficacy at these sites remains controversial. Herein, we eva luated the actions of pindolol at 5-HT1A autoreceptors and specific populat ions of postsynaptic 5-HT1A receptors employing [S-35]GTP gammaS autoradiog raphy, a measure of receptor-mediated G-protein activation. Both 8-OH-DPAT (1 muM) and 5-HT (10 muM) elicited a pronounced increase in [S-35]GTP gamma S binding in the dorsal raphe nucleus, which contains serotonergic cell bod ies bearing 5-HT1A autoreceptors. Pindolol abolished their actions. In the dentate gyrus, lateral septum and entorhinal cortex, structures enriched in postsynaptic 5-HT1A receptors, 8-OH-DPAT (1 muM) and 5-HT (10 muM) also el icited a marked increase in [S-35]GTP gammaS binding which was likewise blo cked by pindolol. The antagonism of 5-HT-induced [S-35]GTP gammaS labelling in the dentate gyrus was shown to be concentration-dependent, yielding a p IC(50) Of 5.82. Pindolol did not, itself, affect [S-35]GTP gammaS binding i n any brain region examined. In conclusion, these data suggest that, as cha racterised by [S-35]GTP gammaS autoradiography, and compared with 5-HT and 8-OH-DPAT, pindolol possesses low efficacy at both pre- and postsynaptic 5- HT1A receptors.