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The cannabinoid antagonist SR141716A facilitates memory acquisition and consolidation in the mouse elevated T-maze.

Takahashi RN, Pamplona FA, Fernandes MS

Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário Trindade, 88049-900 Florianópolis, SC, Brazil. takahashi@farmaco.ufsc.br

Delta9-THC and synthetic cannabinoids produce memory impairment in humans as well as in laboratory animals. The high concentration of cannabinoid CB1 receptors and the presence of endocannabinoids in the hippocampus suggest that a cannabinoid neurochemical system may play a role in learning and memory processes. Thus, the objective of the present work was to study the effect of the cannabinoid antagonist SR141716A (SR) on memory acquisition, consolidation and retrieval in a recently developed elevated T-maze (ETM) model of anxiety and memory. In addition, we investigated whether pre-training SR administration was capable of reversing scopolamine-induced memory impairment. Adult male mice were exposed to the closed arm as many times as necessary for the animals to reach the avoidance criterion of remaining in the closed arm for 300 s; they were then tested (exposed to the closed arm) 24 h and 7 days after the training. SR (0.5, 1.0 or 2.0 mg/kg) was administered i.p. 20 min before the training, immediately after training or 20 min before the test in the mice. The elevated plus-maze (EPM) was used to investigate a possible influence of SR on locomotion and on the anxiety-related behavior. SR provoked memory improvement, which was observed when the drug was administered before (effect on memory acquisition/consolidation) or immediately after the training (effect on memory consolidation), but not when the drug was administered before the test (effect on memory retrieval). Also, SR administration reversed scopolamine-induced amnesia. These effects were observed in the absence of changes in locomotion or anxiety levels. Our results demonstrate that the blockade of cannabinoid receptors may improve memory acquisition and consolidation in the ETM model.

Published 2 May 2005 in Neurosci Lett, 380(3): 270-5.
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