Cannabinoid1 receptors in the hippocampus mediate the deleterious effects of cannabinoid agonists on spatial memory assessed in the radial arm maze

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The present study tested the hypothesis that the disruption of spatial working memory following cannabinoid (CB) agonist administration is mediated by CB1 receptors in the hippocampus. We first tested whether intrahippocampal administration (IHA) of the CB1 receptor agonist CP 55,940 disrupts memory in the radial arm maze and if this effect is blocked by IHA of the CB1 antagonist rimonabant (RIM). We then assessed whether IHA of RIM blocks the memory disrupting effects of systemically administered (i.p.) CP 55, 940 in the radial arm maze as well as in the tetrad (hypothermia, reduced locomotion, antinociception, and catalepsy). Finally, we assessed whether IHA of RIM blocks the memory disrupting effects of systemically administered (i.p.) THC, the main psychoactive substance in marijuana. It was found that IHA of RIM significantly reduced the number of re‐entry errors in the radial arm maze following IHA or systemic administration of CP 55, 940 but did not the block the effects of CP 55,940 in the tetrad suggesting that IHA of RIM selectively blocks the memory disrupting effects of CP 55, 940. IHA of RIM also reduced errors following systemic THC administration. These findings support the hypothesis that hippocampal CB1 receptors have an important role in mediating the memory impairing effects of cannabinoid agonists. This research was supported by the National Institute on Drug Abuse (DA015683 and T23DA07027).