COMPLETE ADAPTATION TO THE MEMORY DISRUPTIVE EFFECTS OF DELTA-9-THC FOLLOWING 35 DAYS OF EXPOSURE

The effects of chronic exposure to the psychoactive cannabinoid deriva tive delta-9-THC were evaluated on a spatial discrimination version of a delayed-match-to-sample (DMTS), short-term memory task in rats. An initially severe disruption of DMTS performance, produced by injection s of 10 mg/kg delta-9-THC immediately prior to the session, was comple tely eliminated following 30-35 days of continuous exposure to the dru g. The timecourse of adaptation to the disruptive effects of delta-9-T HC were characterized and analyzed. Performance at the shortest delay intervals (1-5 sec) was reduced least during the 35 day exposure. At d elays longer than 5 sec, performance was severely reduced to near chan ce levels upon initial exposure. Performance recovered systematically over the 35 day exposure period to criterion levels. Recovery between days 5-16 of exposure was most pronounced at delays of 6-20 sec, after which (days 17-30) recovery at all delays occurred at the same rate. Withdrawal from the drug after the 35 day exposure produced a slight b ut significant reduction in performance at all delays which dissipated within 2 days. There were no subsequent residual effects of the 35 da y exposure on DMTS performance measured up to 15 days after withdrawal from drug treatment. These results suggest that the effects of cannab inoid substances on short-term memory are consistent with those produc ed by damage to the hippocampus in this same task, and that adaptation to an initial debilitating dose was consistent with recovery from a h ippocampal deficit. Upon repeated exposure, performance returned to cr iterion levels even though the high dose and drug concentration were s imilar to when performance was severely disrupted. It is therefore pos sible that cannabinoid induced disruption of DMTS performance was susc eptible to changes in receptor-coupled biochemical systems (1) that me diated adaptation to the deleterious effects of delta-9-THC.