Differential effects of Δ9-THC on spatial reference and working memory in mice

• Published in: Psychopharmacologia Vol. 157; no. 2; pp. 142 - 150
• Main Authors: VARVEL, S. A, HAMM, R. J, MARTIN, B. R, LICHTMAN, A. H
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.09.2001; Springer Nature B.V
• Subjects: Biological and medical sciences; Cannabinoid CB1 receptors; Cannabinoids; Cannabis; Catalepsy; Drug addictions; Hypothermia; Medical sciences; Memory; Mental task performance; Motor task performance; Pain perception; Phencyclidine; Scopolamine; Short term memory; Spatial memory; Tetrahydrocannabinol; THC; Toxicology; Reference memory; Cognitive disorder; Toxicity; Catalepsy; Cognition; Glutamate receptor; Cannabinoid; Cholinergic receptor; Subcutaneous administration; Drug of abuse; Antagonist; Mechanism of action; Biological receptor; Nociception; Illicit drug; Rodentia; Locomotion; Vertebrata; Mammalia; Mouse; Animal; Working memory; NMDA receptor; Hypothermia; Spatial memory
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s002130100780

Rationale: Marijuana remains the most widely used illicit drug in the U.S., and recent attention has been given to putative therapeutic uses of marijuana and cannabinoid derivatives. Thus, developing a better understanding of Δ9-THC (tetrahydrocannabinol)-induced mnemonic deficits is of critical importance. Objectives: These experiments were conducted to determine whether Δ9-THC has differential effects on spatial reference and working memory tasks, to investigate its receptor mechanism of action, and to compare these effects with those produced by two other compounds – scopolamine and phencyclidine – known to produce mnemonic deficits. In addition, the potency of Δ9-THC in these memory tasks was compared with its potency in other pharmacological effects traditionally associated with cannabinoid activity. Methods: Two different versions of the Morris water maze were employed: a working memory task and a reference memory task. Other effects of Δ9-THC were assessed using standard tests of hypomotility, antinociception, catalepsy, and hypothermia. Results: Δ9-THC disrupted performance of the working memory task (3.0 mg/kg) at doses lower than those required to disrupt performance of the reference memory task (100 mg/kg), or elicit hypomotility, antinociception, catalepsy, and hypothermia. These performance deficits were reversed by SR 141716A. The effects of Δ9-THC resembled those of scopolamine, which also selectively disrupted the working maze task. Conversely, phencyclidine disrupted both tasks only at a dose that also produced motor deficits. Conclusions: These data indicate that Δ9-THC selectively impairs performance of a working memory task through a CB1 receptor mechanism of action and that these memory disruptions are more sensitive than other pharmacological effects of Δ9-THC.