Enhancement of cortical and hippocampal cholinergic neurotransmission through 5-HT1A receptor-mediated pathways by BAY x 3702 in freely moving rats

Involvment of serotonin (5-HT) in the regulation of cholinergic neuronal activity by modulation of acetylcholine (ACh) release has been reported for various regions of the brain. Cortical and hippocampal cholinergic neurotransmission is of particular importance in the mechanisms of attention as well as learning and memory. In the present study, we investigated the effect of R-(-)-2-{4-[(chroman-2-ylmethyl)-amino-butyl}-1, 1-dioxo-benzo[d]isothiazolone hydrochloride (BAYx3702), a novel, high-affinity 5-HT1A receptor agonist on ACh release in the cerebral cortex and hippocampus of freely moving rats using an in vivo microdialysis technique. Acetylcholine efflux from the cortex and hippocampus was measured every 30 m using a sensitive and specific radioimmunoassay and was stable for at least 5 h. The ACh efflux from the cortex and hippocampus was increased significantly by BAY x 3702 (0.3 mg/kg, i.p.) compared with saline administration. WAY-100635 (0.6 mg/kg, s.c.), a selective 5-HT1A receptor antagonist, eliminated the augmentation of ACh efflux induced by BAY x 3702 in both brain regions. These results demonstrate that stimulation by BAY x 3702 enhanced ACh release in both the cortex and hippocampus through 5-HT1A receptor-mediated pathways. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.