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Paul Mallet

The endogenous cannabinoid receptor agonist anandamide impairs memory in rats

Behavioural Pharmacology, 7, 276-284.
Mallet, P.E. & Beninger, R.J.

published: 1996 | Research publication | Journal article

Abstract: Anandamide recently was discovered to be an endogenous substance that acts as an agonist at cannabinoid receptors in the central nervous system.  Because exogenous cannabinoids such as ?9-tetrahydrocannabinol (?9–THC), the principle psychoactive ingredient of marijuana, have been found to impair memory, we undertook the present study to examine the mnemonic effects of anandamide.  Memory was assessed in rats well-trained in a two-component instrumental discrimination task with a conditional discrimination to test reference memory and a delayed nonmatch-to-position to test working memory.  Since anandamide has a short metabolic half-life, we examined the mnemonic effects of anandamide (0.0-2.0 mg/kg) in rats pre-treated with the protease inhibitor phenylmethylsulfonyl fluoride (2.0 mg/kg), serving to increase the metabolic half-life of anandamide.  Under these conditions, a dose-dependent impairment of the nonmatch-to-position, but not the conditional discrimination component was found, closely resembling that observed following ?9–THC.  This is the first report that anandamide impairs memory; results suggest that endogenous cannabinoids may be involved in cognitive processes influencing memory. 

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revised Jan 24/06

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