EFFECT OF NMDA-ANTAGONISTS ON RAPID TOLERANCE TO ETHANOL UNDER 2 DIFFERENT TESTING PARADIGMS

We have recently reported that pretreatment with NMDA receptor antagon ists [(+)MK-801 and ketamine] inhibited the development of rapid toler ance to ethanol hypothermia and motor-impairment on day 2 in animals r eceiving ethanol on day 1, compared to the control group pre treated w ith saline. In these studies rats were tested at 30, 60, 90 and 120 mi n after ethanol on both day 1 and 2. In the present report we compared the development of rapid tolerance under 2 different conditions: (1) in groups of rats that were tested on the tilt-plane at all test times (Testing or Intoxicated Practice group), (2) in groups of rats that w ere not tested on the tilt-plane but were handled at all test times on day 1 (dummy testing). Rats were pretreated with ethanol or saline on day 1 and tested with ethanol on day 2 in all the above studies. Both testing (intoxicated practice) and dummy testing of animals on day 1 after pretreatment with ethanol produced rapid tolerance to ethanol on day 2. However, (+)MK-801 or ketamine pretreatment, which blocked rap id tolerance in the intoxicated practice testing paradigm, failed to b lock rapid tolerance in the dummy testing paradigm. Similar results we re obtained for rapid tolerance and for the effect of ketamine in the hypothermia experiment. These findings suggest that NMDA antagonists b lock rapid tolerance in the intoxicated testing paradigm but not in th e dummy testing paradigm. However, whether the two types of rapid tole rance tested in the present experiments are indeed different or interr elated remains to be further investigated. (C) 1997 Elsevier Science I nc.