Recovery from impaired working memory performance during chronic Δ-9-tetrahydrocannabinol administration to adolescent rhesus monkeys.

Abstract

The relationship between adolescent cannabis use and susceptibility to persistent cognitive impairments is poorly understood. We examined the effects of repeated exposure to Δ-9-tetrahydrocannabinol (THC) on reinforcement-related learning and performance of spatial working memory (WM) tasks of varying difficulty in adolescent monkeys. Seven pairs of male adolescent rhesus monkeys, matched for baseline cognitive performance, received vehicle or THC intravenously 5 days/week for 12 months. Performance on 4-item spatial WM trials was assessed throughout the 12-month study period. At the 6-month time point, more difficult novel and distractor 8-item spatial WM trials were added. Residual effects on performance were determined 23 or 71 h after THC or vehicle administration throughout the study. Relative to vehicle-exposed animals, repeated THC exposure was initially associated with significantly slower improvement in performance accuracy on 4-item spatial WM trials; however, this performance difference gradually diminished such that by month 12, accuracy did not significantly differ between vehicle and THC groups. Similarly, for the novel and distractor 8-item trials introduced at month 6, performance accuracy improved more slowly in the THC than in the vehicle group, despite comparable performance between groups on the 4-item task during this same period. These findings suggest that compared to vehicle exposure, THC exposure during adolescence impairs the reinforcement-related learning process required for improved performance on spatial WM tasks, but this impairment might be overcome with continued training, even in the face of ongoing THC exposure.