Prior and delayed applications of dizocilpine or ethanol alter locomotor sensitization to morphine

Three experiments compared the effects of prior versus delayed applications of dizocilpine (MK-801), a noncompetitive NMDA antagonist, to ethanol, a p utative NMDA antagonist, on morphine locomotor activity. In Experiment 1, r ats received MK-801 (0.1 mg/kg), ethanol (1 g/kg), or vehicle injections 30 min prior to morphine (0 or 10 mg/kg) injections for 14 days. The expressi on of morphine (0 or 3 mg/kg) locomotor sensitization was assessed 1 week l ater. Both MK-801 and ethanol attenuated morphine-induced locomotor activit y. Chronic MK-801 with or without morphine eliminated morphine's temporal p attern of activity calling into question the specificity of its effect on s ensitization. In contrast, chronic ethanol administration attenuated morphi ne locomotor sensitization. In Experiment 2, the effects of the agents on t he acute biphasic locomotor effects of morphine (hypoactivity followed by h yperactivity) were examined. Agents were administered 30 min prior to or 12 0 min after morphine (or vehicle). Neither agent at either administration t ime altered morphine's acute locomotor effects. In Experiment 3, the effect s of chronic delayed application of MK-801 or ethanol (120-min post-morphin e administration for 14 days) on the expression of morphine locomotor sensi tization were assessed. Results were similar to the prior application effec ts of Experiment 1. These data suggest that the delayed effects of morphine are important in changes seen with chronic administration and these may in volve NMDA receptor activation. Further, in conjunction with our previous w ork, ethanol appears to alter plasticity effects of chronic morphine admini stration perhaps via its NMDA antagonist effects. (C) 2000 Elsevier Science B.V. All rights reserved.