5‐HT1 agonists reduce 5‐hydroxytryptamine release in rat hippocampus in vivo as determined by brain microdialysis

Abstract

An intracerebral perfusion method, brain microdialysis, was used to assess changes of 5‐hydroxytryptamine (5‐HT) release in the ventral hippocampus of the chloral hydrate‐anaesthetized rat in response to systemic administration of a variety of 5‐HT1 receptor agonists. A stable output of reliably detectable endogenous 5‐HT was measured in dialysates collected from ventral hippocampus with the 5‐HT reuptake inhibitor, citalopram, present in the perfusion medium. Under these conditions the putative 5‐HT1A agonist 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin (8‐OH‐DPAT) caused a dose‐dependent (5–250 μg kg−1, s.c.) reduction of 5‐HT in hippocampal dialysates. Similarly, the putative 5‐HT1A agonists gepirone (5 mg kg−1, s.c.), ipsapirone (5 mg kg−1, s.c.) and buspirone (5 mg kg−1, s.c.) markedly reduced levels of 5‐HT in hippocampal perfusates whereas their common metabolite 1‐(2‐pyrimidinyl) piperazine (5 mg kg−1, s.c.), which does not bind to central 5‐HT1A recognition sites, had no effect. 5‐Methoxy‐3‐(1,2,3,6‐tetrahydro‐4‐pyridinyl)‐lH‐indole (RU 24969), a drug with reported high affinity for brain 5‐HT1B binding sites, also produced a dose‐dependent (0.25–5 mg kg−1, s.c.) decrease of hippocampal 5‐HT output. These data are direct biochemical evidence that systemically administered putative 5‐HT1A and 5‐HT1B agonists markedly inhibit 5‐HT release in rat ventral hippocampus in vivo. 1989 British Pharmacological Society