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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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