CHRONIC TREATMENT WITH MK-801 DECREASES D2 DOPAMINE RECEPTOR FUNCTION IN RAT STRIATUM

Present results show that a single treatment with dizocilpine (MK-801, 0.25 mg/kg IP) failed to modify the specific binding to D1 or D2 DA receptors. In contrast, repeated administrations for 3 weeks resulted in a statistically significant decrease of [H-3]Spiroperidol binding to cortical or striatal membranes but did not change the number or the apparent affinity of [H-3]MK-801 binding in well-washed cortical membranes. Consistent reduction in specific D2 receptor mediated behavior was obtained. The data suggest that the changes in DAergic function following repeated administrations with MK-801 could be suggestive of potential therapeutic uses of negative allosteric drugs in some DA related disfunctions.