DIZOCILPINE PREVENTS THE DEVELOPMENT OF TOLERANCE TO ETHANOL-INDUCED ERROR ON A CIRCULAR MAZE TEST

Dizocilpine [(+)MK-801] and ketamine, in doses that disrupt learning a nd memory, also prevent the development of tolerance to the motor impa iring effects of ethanol (EtOH). However, dizocilpine itself affects m otor behavior. In order to separate the possible influence of these tw o effects on the development of tolerance to EtOH, food-reinforced per formance on a circular maze test was used in two different experiments . EtOH alone (1.2 g/kg) tended to increase the error score and reduce number of runs per trial, running speed, and total distance run, but o n chronic administration of EtOH, tolerance developed progressively to all these effects. Dizocilpine also increased the error score, but ha d a biphasic effect on measures of running: low and intermediate doses (0.009 and 0.075 mg/kg, IP) increased running distance, whereas a hig h dose (0.15 mg/kg) decreased running speed and distance. When combine d with EtOH, dizocilpine tended to overcome the effect of EtOH on runn ing activity, but not on error score. Chronically, dizocilpine (0.075 and 0.15 mg/kg) prevented the development of tolerance to the effect o f EtOH on error score, even though the lower dose of dizocilpine permi tted tolerance to the effects of EtOH on running. These results sugges t that NMDA receptor antagonists selectively inhibit tolerance to cogn itive effects of ethanol even when the antagonists do not affect motor performance.