MK-801 blocks the development of behavioral sensitization to ethanol

Background: Studies have indicated that MK-801 (a noncompetitive N-methyl-D-aspartate receptor antagonist) participates in the long-term neural changes responsible for sensitization to stimulant drugs. It is known that repeated administration of low doses of ethanol sensitizes animals to its stimulant effect. In this work we investigated whether MK-801 alters the development of behavioral sensitization to ethanol. Methods: Groups of male Swiss mice were treated with saline or ethanol (2.0 g/kg) plus saline or MK-801 (0.25 mg/kg) for 21 days. On day 25, all animals received an ethanol challenge injection (2.0 g/kg). We measured locomotor activity on days 1, 7, 14, 21 and 25. In addition, we assessed the effects of different doses of MK-801 on the response to a low dose of ethanol (2.0 g/kg). Results: Ethanol-treated mice developed sensitization to the locomotor-stimulating effect of the drug, whereas those concomitantly receiving ethanol and MK-801 did nut. All doses of MK-801 that were used stimulated the locomotor activity of both ethanol and saline-treated animals. Conclusions: The findings support the hypothesis that N-methyl-D-aspartate receptors have an important role in the development of sensitization to drugs of abuse.