SR 141716A prevents Δ9-tetrahydrocannabinol-induced spatial learning deficit in a Morris-type water maze in mice

This study reports a series of spatial discrimination procedures in a Morris-type maze to investigate the effects of Delta (9)-tetrahydrocannabinol (Delta (9)-THC) on different phases of learning and memory in mice. Adult male mice were given training trails to find the submerged platform at a fixed location in the water maze adapted for mice, In additional experiments, mice were trained with the repeated acquisition procedure to test the working memory. Results indicate that Delta (9)-THC (8 mg/kg ip) 30 min pretest impaired specifically the acquisition of spatial learning and the performance of mice in the working memory task, while consolidation and retrieval of a previously teamed task were not affected. There was no evidence of motoric difficulty, as the number of quadrant line crossings was not decreased and no visible sign of sensorimotor disturbance was observed during swimming. Pretreatment with SR 141716A (1 mg/kg ip), a CB1 cannabinoid receptor antagonist, significantly prevented the teaming deficits in the water maze. These findings show that Delta (9)-THC impairs spatial discrimination learning in a selective way in the water maze in mice and that these deficits may be mediated by cannabinoid receptors. (C) 2001 Elsevier Science Inc. All rights reserved.