The serotonin1A receptor partial agonist S 15535 [4-(benzodioxan-5yl)l-(indan-2-yl)piperazine] enhances cholinergic transmission and cognitive function in rodents: a combined neurochemical and behavioral

These studies examined the influence of the selective 5-hydroxy-tryptamine (serotonin) (5-HT)1A receptor partial agonist S15535 [4-(benzodioxan-5-yl)1-(indan-2-yl)piperazine] upon cholinergic transmission and cognitive function in rodents. In the absence of acetylcholinesterase inhibitors, S15535 dose-dependently (0.04– 5.0 mg/kg s.c.) elevated dialysis levels of acetylcholine in the frontal cortex and dorsal hippocampus of freely moving rats. In the cortex, the selective 5-HT1A receptor antagonist WAY100,635 [(N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2-pyridinyl) cyclo-hexanecarboxamide) fumarate] dose-dependently (0.0025– 0.63) blocked this action of S15535. By contrast, in dorsal hip-pocampus, WAY100,635 mimicked the induction of acetylcholine release by S15535. In a social recognition paradigm, S15535 dose-dependently (0.16–10.0) improved retention, an actio