Cannabinoid CB1 receptor-mediated impairment of visuospatial attention in the rat

Rationale: CB1 receptors (CB1Rs) mediate many of the psychoactive effects of cannabinoids, and marijuana intoxication can produce neurocognitive deficits with a similarity to those seen in schizophrenia, including impairments of attention. Objectives: We thus sought to characterize the effects of a CB1R-selective agonist and antagonist on attention in the rat using a lateralized reaction time task (LRT). We hypothesized that CB1R agonists would impair performance and that CB1R antagonists might improve performance. Methods: Subjects were trained to perform the LRT, a procedure that measured their ability to attend to and detect brief visual target stimuli. After training, we tested the effects of the CB1R agonist WIN55,212- 2 ( WIN; 0 - 2.5 mg/kg) or the CB1R antagonist SR141716A (SR; 0 - 1.0 mg/kg), administered alone or in combination, on visual attention performance using task conditions in which target stimulus salience was varied systematically across trials. Results: The highest dose of WIN reduced correct choices in well-trained rats, with impairment greatest at the shortest stimulus durations. The highest dose of WIN also increased omissions and slowed response times. By contrast, SR itself did not produce any measurable effects on performance but was able to prevent the impairment produced by WIN. Conclusions: These results suggest that CB1Rs mediate the attentional performance impairments caused by acute administration of cannabinoid agonists and begin to unravel the possible contribution of cannabinoid systems to the pathophysiological substrates of cognitive dysfunction in schizophrenia.