TOLERANCE DEVELOPS TO THE SPATIAL-LEARNING DEFICIT PRODUCED BY DIAZEPAM IN RATS

The present experiment sought to determine in rats if 1) tolerance dev elops to the amnesic effect of diazepam after chronic treatment, 2) th e sedative and amnesic effects of diazepam can be dissociated via diff erential rates of tolerance development, and 3) withdrawal from long-t erm diazepam treatment affects mnemonic processes. Rats were given dia zepam (3 mg/kg) acutely or chronically for 5, 15, or 30 d prior to beh avioral testing. Sedation was assessed as exploratory activity in an o pen field and amnesia was assessed as spatial learning in the Morris w ater maze. Tolerance to the sedative effect of diazepam was exhibited after 5 d pretreatment whereas tolerance to the amnesic effect of diaz epam was exhibited only after 30 d pretreatment. Withdrawal from diaze pam produced a transitory and mild disruption of spatial learning. The data demonstrate 1) tolerance can develop to the amnesic effect of di azepam with extended treatment, 2) the sedative and amnesic effects of diazepam are largely independent, and 3) withdrawal from chronic diaz epam treatment can retard optimal learning. Copyright (C) 1997 Elsevie r Science Inc.