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 change s responsible for sensitization to stimulant drugs. It is known that repeat ed administration of low doses of ethanol sensitizes animals to its stimula nt effect. In this work we investigated whether MK-801 alters the developme nt 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 anima ls received an ethanol challenge injection (2.0 g/kg). We measured locomoto r activity on days 1, 7, 14, 21 and 25. In addition, we assessed the effect s 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-stim ulating effect of the drug, whereas those concomitantly receiving ethanol a nd MK-801 did nut. All doses of MK-801 that were used stimulated the locomo tor 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 dru gs of abuse.