Abstract
Marijuana (Cannabis sativa) and its primary psychoactive component, δ-9-tetrahydrocannabinol (Δ9-THC), have long been known to disrupt cognition in humans. Although Δ9-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 Δ9-THC on acquisition versus memory retrieval in a mouse repeated acquisition Morris water-maze task. To distinguish between these processes, subjects were administered Δ9-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 Δ9-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 Δ9-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.
Footnotes
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This work was supported by National Institute on Drug Abuse Grants DA015683 and DA002396.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.107.119594.
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ABBREVIATIONS: Δ9-THC, Δ9-tetrahyrocannabinol; CB1, cannabinoid-1 receptor; HU-210, Δ8-tetrahydrocannabinol dimethyl heptyl; NMDA, N-methyl-d-aspartate; MK-801, 5H-dibenzo[a,d]cyclohepten-5,10-imine (dizocilpine maleate); rimonabant, SR141716, N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HCl; ANOVA, analysis of variance; CI, confidence interval; CP 55,940, (1R,3R,4R)-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-4-(3-hydroxypropyl)cyclohexan-1-ol; WIN-55,212-2, R-(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)]-pyrolol[1,2,3de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone.
- Received January 8, 2007.
- Accepted June 22, 2007.
- The American Society for Pharmacology and Experimental Therapeutics
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