Behavioral and histological effects of chronic antipsychotic and antidepressant drug treatment in aged rats with focal ischemic brain injury.

Psychotropic drugs are commonly used in the elderly, including those who may sustain ischemic attacks. Concomitant CNS medication may interfere with functional recovery. The present study evaluated the effect of risperidone, an atypical neuroleptic, and fluoxetine, a selective serotonin reuptake inhibitor, on histological and functional outcome after experimental stroke in aged rats, which might be more vulnerable to brain insults. Aged Wistar rats were treated with risperidone at a dose of 1 mg/kg (i.p., once a day), fluoxetine at a dose of 5 mg/kg (i.p., once a day), or their combination. Drug treatment was started 7 days before focal cortical photothrombosis (Rose Bengal, 20 mg/kg) and continued for 28 days thereafter. Sensorimotor recovery was assessed by a new beam-walking test and spatial learning by the Morris water-maze before cortical stroke, immediately after stroke, and at the end of follow-up. Infarct volumes were measured from nitroblue tetrazolium-stained sections at the end of follow-up. The high slip ratio for the contralateral hindlimb in ischemic rats treated with risperidone indicated sensorimotor impairment when tested 2 h after drug administration. Sensorimotor impairment was not observed, however, when the rats were tested 24 h after risperidone administration. Similarly, water-maze performance was impaired 2 h after risperidone. Fluoxetine did not affect sensorimotor or water-maze performance. Cortical infarct volumes were not different in ischemic controls and ischemic rats treated with antipsychotic drugs. The present study showed that an atypical neuroleptic, risperidone, acutely impairs behavioral performance, but does not affect histological or functional outcome in aged rats subjected to cortical photothrombosis.