title: Δ⁹Tetrahydrocannabinol impairs visuo-spatial associative learning and spatial working memory in rhesus macaques.
abstract: Cannabis remains the most commonly abused illicit drug and is rapidly expanding in quasi-licit use in some jurisdictions under medical marijuana laws. Effects of the psychoactive constituent Δ⁹tetrahydrocannabinol (Δ⁹THC) on cognitive function remain of pressing concern. Prior studies in monkeys have not shown consistent evidence of memory-specific effects of Δ⁹THC on recognition tasks, and it remains unclear to what extent Δ⁹THC causes sedative versus specific cognitive effects. In this study, adult male rhesus monkeys were trained on tasks which assess spatial working memory, visuo-spatial associative memory and learning as well as motivation for food reward. Subjects were subsequently challenged with 0.1-0.3 mg/kg Δ⁹THC, i.m., in randomized order and evaluated on the behavioral measures. The performance of both vsPAL and SOSS tasks was impaired by Δ⁹THC in a dose and task-difficulty dependent manner. It is concluded that Δ⁹THC disrupts cognition in a way that is consistent with a direct effect on memory. There was evidence for interference with spatial working memory, visuo-spatial associative memory and incremental learning in the latter task. These results and the lack of specific effect of Δ⁹THC in prior visual recognition studies imply a sensitivity of spatial memory processing and/or working memory to endocannabinoid perturbation.
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA. mtaffe@scripps.edu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Taffe
mesh_terms: D000818:Animals; D001245:Association Learning / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D063386:Cannabinoid Receptor Agonists / Q000633:toxicity*; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000209:etiology; D013759:Dronabinol / Q000633:toxicity*; D008253:Macaca mulatta; D008297:Male; D008569:Memory Disorders / Q000209:etiology; D008570:Memory, Short-Term / Q000187:drug effects; D009048:Motor Skills / Q000187:drug effects; D019957:Motor Skills Disorders / Q000209:etiology; D020258:Neurotoxicity Syndromes / Q000503:physiopathology*; D010364:Pattern Recognition, Visual / Q000187:drug effects; D011619:Psychotropic Drugs / Q000633:toxicity*; D011897:Random Allocation; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists; D013037:Spatial Behavior / Q000187:drug effects*; D014796:Visual Perception / Q000187:drug effects*
chemical_list: D063386:Cannabinoid Receptor Agonists; D011619:Psychotropic Drugs; D043884:Receptor, Cannabinoid, CB1; D013759:Dronabinol