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BEHAVIORAL PHARMACOLOGY

Exposure to Marijuana Smoke Impairs Memory Retrieval in Mice

Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia

Marijuana (Cannabis sativa) and its primary psychoactive component, -9-tetrahydrocannabinol (⁹-THC), have long been known to disrupt cognition in humans. Although ⁹-THC and other cannabinoids disrupt performance in a wide range of animal models of learning and memory, few studies have investigated the effects of smoked marijuana in these paradigms. Moreover, in preclinical studies, cannabinoids are generally administered before acquisition, and because retention is generally evaluated soon afterward, it is difficult to distinguish between processes related to acquisition and retrieval. In the present study, we investigated the specific effects of marijuana smoke and injected ⁹-THC on acquisition versus memory retrieval in a mouse repeated acquisition Morris water-maze task. To distinguish between these processes, subjects were administered ⁹-THC or they were exposed to marijuana smoke either 30 min before acquisition or 30 min before the retention test. Inhalation of marijuana smoke or injected ⁹-THC impaired the ability of the mice to learn the location of the hidden platform and to recall the platform location once learning had already taken place. In contrast, neither drug impaired performance in a cued task in which the platform was made visible. Finally, the cannabinoid-1 (CB₁) receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HCl (rimonabant) blocked the memory disruptive effects of both ⁹-THC and marijuana. These data represent the first evidence demonstrating that marijuana impairs memory retrieval through a CB₁ receptor mechanism of action and independently of its effects on sensorimotor performance, motivation, and initial acquisition.

Address correspondence to: Dr. Aron H. Lichtman, Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Box 980613, Richmond, VA 23298-0613. E-mail: alichtma{at}vcu.edu