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

1 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. 2 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. 3 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. 4 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 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. 6 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.