Autoradiographic studies of 5‐HT 1A ‐receptor‐stimulated [ 35 S]GTPγS‐binding responses in the human and monkey brain

G‐protein activation mediated by serotonin 5‐HT 1A receptors in human and monkey brain was investigated by using quantitative autoradiography of agonist‐stimulated [ 35 S]GTPγS binding to whole‐hemisphere brain sections. [ 35 S]GTPγS binding was stimulated by the mixed 5‐HT 1A/1B/1D agonist L 694247 (10 μ m ) in human brain regions enriched in 5‐HT 1A binding sites [e.g. hippocampus (132–137%), superficial layers of the neocortex (37–61%), and cingulate and entorhinal cortex (34 and 32%, respectively)]. L 694247 caused virtually no stimulation in regions with 5‐HT 1B/1D receptors, such as substantia nigra, caudate nucleus and putamen. Similar results were obtained with monkey brain sections. The L 694247‐mediated [ 35 S]GTPγS‐binding responses in human and monkey brain sections were antagonized by the selective, silent 5‐HT 1A antagonist WAY 100635 (10 μ m ). The 5‐HT 1B inverse agonist SB 224289 (10 μ m ) did not affect the [ 35 S]GTPγS‐binding response of L 694247. The distribution pattern of the [ 35 S]GTPγS‐binding response and the antagonist profile suggest the L 694247‐induced response in human and monkey brain is mediated by 5‐HT 1A receptors. A weak stimulation of [ 35 S]GTPγS binding was also observed in human hippocampus with either 10 μ m 8‐OH‐DPAT (25 ± 4%) or naratriptan (42 ± 2%) compared with that obtained with L 694247. In conclusion, G‐protein activation by 5‐HT 1A receptors can be measured in human and monkey brain sections. L 694247 appears to possess higher efficacy at 5‐HT 1A receptors compared with 8‐OH‐DPAT and naratriptan.