Stimulation of 5-HT1A receptors reduces apoptosis after transient forebrain ischemia in the rat

It has recently been shown that 5-HT1A receptor stimulation reduced the infarct volume after occlusion of the middle cerebral artery in rats. Since then is increasing evidence that apoptosis is involved in neurodegenerative diseases and stroke, we investigated whether the 5-HT1A agonist Bay x 3702 could protect neurons against apoptotic damage in a rat model of transient forebrain cerebral ischemia. Bay x 3702 (4 mug/kg i.v.) caused a 10% reduction of neuronal damage in the hippocampal CA1 subfield. Higher doses of Bay x 3702 (40 and 12 mug/kg i.v.) did not cause any neuroprotective effect, most likely because of the strong reduction of mean arterial blood pressure during the period of Bay x 3702 infusion. Bay x 3702 (4 mug/kg i.v.) diminished DNA laddering in the hippocampus and striatum 4 days after 10 min forebrain ischemia. These results were confirmed by TUNEL-staining. The anti-apoptotic effect was abolished by additional treatment with the 5-HT1A receptor antagonist WAY 100635 (1 mg/kg). Taken together, the results suggest that Bay x 3702 can rescue hippocampal as well as striatal neurons from apoptotic cell death in vi iio via stimulation of 5-HT1A receptors. (C) 2000 Elsevier Science B.V. All rights reserved.