Sensitization to the locomotor stimulant effect of cocaine modifies the binding of [3H]MK-801 to brain regions and spinal cord of the mouse

The effects of chronic administration of cocaine and its subsequent withdrawal on the binding of [H-3]MK-801, an antagonist of the N-methyl-D-aspartate (NMDA) receptor, to brain regions and spinal cord of the mouse was determined. Chronic administration of cocaine (10 mg/kg, SC) twice a day for 7 days sensitized male Swiss-Weber mice to its locomotor activity, as evidenced by a greater locomotor activity in comparison with vehicle-injected controls. In nonwithdrawing mice, the binding of [H-3]MK-801 was increased in the cerebellum and spinal cord but was decreased in the cortex and hypothalamus. On the other hand, during withdrawal from cocaine, a significant decrease in the binding of [H-3]MK-801 was observed only in the cortex, but the changes in the cerebellum, spinal cord and hypothalamus were normalized. It is concluded that, in the mouse, sensitization to the locomotor activating action of cocaine is associated with differential changes in the NMDA receptors of the central nervous system. (C) 1999 Elsevier Science Inc. All rights reserved.