EFFECT OF NMDA ANTAGONISTS ON RAPID TOLERANCE TO BENZODIAZEPINES

We have reexamined the effect of NMDA antagonists [(+)MK-801 and ketam ine] on rapid tolerance to chlordiazepoxide, (+)MK-801 and ketamine bl ocked the development of rapid tolerance to chlordiazepoxide, but this effect was dependent on the dose ratio of the NMDA antagonist to that of the benzodiazepine used to produce rapid tolerance, Furthermore, N MDA antagonists blocked both learned and unlearned tolerance to chlord iazepoxide. It appears that in addition to impairment of memory and le arning, NMDA antagonists may also influence some other mechanism invol ved in the production of drug tolerance. Copyright (C) 1997 Elsevier S cience Inc.