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 inf arct volume after occlusion of the middle cerebral artery in rats. Since th en is increasing evidence that apoptosis is involved in neurodegenerative d iseases and stroke, we investigated whether the 5-HT1A agonist Bay x 3702 c ould protect neurons against apoptotic damage in a rat model of transient f orebrain cerebral ischemia. Bay x 3702 (4 mug/kg i.v.) caused a 10% reducti on 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, mo st likely because of the strong reduction of mean arterial blood pressure d uring the period of Bay x 3702 infusion. Bay x 3702 (4 mug/kg i.v.) diminis hed DNA laddering in the hippocampus and striatum 4 days after 10 min foreb rain ischemia. These results were confirmed by TUNEL-staining. The anti-apo ptotic effect was abolished by additional treatment with the 5-HT1A recepto r antagonist WAY 100635 (1 mg/kg). Taken together, the results suggest that Bay x 3702 can rescue hippocampal as well as striatal neurons from apoptot ic cell death in vi iio via stimulation of 5-HT1A receptors. (C) 2000 Elsev ier Science B.V. All rights reserved.