Strain-dependent effects of anandamide on memory consolidation in mice areantagonized by naltrexone

Post training administration of anandamide (1.5, 3, 6 mg/kg) dose-dependent ly impaired retention of an inhibitory avoidance response in DBA/2 mice, wh ile improving it in C57BW6 mice. The effects on retention performance induc ed by the drug appear to be due to an effect on memory consolidation. They were observed when drug was given at short, but not long, periods of time a fter training, i.e. when the memory trace was susceptible to modulation. Th ese effects of anandamide parallel those of opioid agonists, as previously reported. Moreover, the opioid antagonist naltrexone improved retention in DBA/2 mice, while impairing it in C57BL/6 mice. Pre-treatment with the opio id antagonist at a non-effective dose (0.1 mg/kg) antagonized the effects o f anandamide on memory consolidation in both strains. These results strongl y suggest that endogenous cannabinoids affect memory processes through opio id systems. The possible involvement of other neurotransmitter systems, suc h as dopamine, in strain-dependent effects of anandamide in memory consolid ation is discussed. (C) 1999 Lippincott Williams & Wilkins.