MK-801 POTENTIATES ETHANOLS EFFECTS ON LOCOMOTOR-ACTIVITY IN MICE

FAST vs. SLOW selected mouse lines and C57BL/6J (B6) vs. DBA/2J (D2) i nbred strains differ in their sensitivities to ethanol's locomotor sti mulant effects, and provide two unique sets of genetic animal models t o study neurophysiological substrates of this behavior. To determine w hether NMDA receptor function mediates sensitivity to ethanol's stimul ant effects, we assessed the effects of the noncompetitive NMDA antago nist, MK-801, on locomotor activity of naive and ethanol-treated FAST, SLOW, B6, and D2 mice. MK-801 (0.01-0.5 mg/kg, IP) had biphasic effec ts in all genotypes, with stimulation at moderate doses and decreased activation at the highest dose. FAST mice were more activated by MK-80 1 than SLOW mice, suggesting that selection differentially altered NMD A receptor function between the lines. B6 and D2 mice did not differ i n locomotor responses following MK-801 administration. Stimulant doses of MK-801 decreased or blocked ethanol-stimulated locomotor activity in FAST and D2 mice, and potentiated the locomotor depressant actions of ethanol in SLOW and B6 mice. Potentiation of ethanol's activating p roperties was observed in one treatment group in D2 mice. These data s uggest that NMDA receptors modulate ethanol's stimulant properties, by a more significant involvement in expression of ethanol's locomotor d epressant properties. (C) 1998 Elsevier Science Inc.