Effects of scopolamine and MK-801 on recovery of function following unilateral lesions of the rat somatic sensorimotor cortex

Abstract

Following brain injury there is an excessive release of glutamate and acetylcholine which may lead to secondary cell death. Previous research has suggested that agents which antagonize glutamatergic and cholinergic receptors may facilitate recovery during a critical period following brain injury. Although research has demonstrated the efficacy of treatment with MK-801 (an NMDA receptor blocker) and scopolamine (a muscarinic antagonist) following injury, few studies have examined the "window of opportunity" or possible combinations of such treatments. Thus, we examined the effects of MK-801 and scopolamine alone and in combination on behavioral recovery following unilateral electrolytic lesions of the rat somatic sensorimotor cortex (SMC). Rats received unilateral lesions in the SMC and a regimen of scopolamine (1 mg/kg, ip), MK-801 (1 mg/kg, ip), MK-801 + scopolamine, or saline at one of three different time intervals (15 min, 2 hrs, 48 hrs) after lesioning. Behavioral tests measured somatosensorimotor asymmetries, locomotor activity on a grid surface, and forelimb placing. Although scopolamine and MK-801 facilitate recovery of function, combined treatment with scopolamine + MK-801 facilitated recovery regardless of type of behavior measured. Therefore, these data support the idea that muscarinic and NMDA receptors may interact to control the pathophysiological responses associated with brain injury.