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

Post-training administration of anandamide (1.5, 3, 6 mg/kg) dose-dependently impaired retention of an inhibitory avoidance response in DBA/2 mice, while improving it in C57BL/6 mice. The effects on retention performance induced 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 after training, i.e. when the memory trace was susceptible to modulation. These 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 opioid antagonist at a non-effective dose (0.1 mg/kg) antagonized the effects of anandamide on memory consolidation in both strains. These results strongly suggest that endogenous cannabinoids affect memory processes through opioid systems. The possible involvement of other neurotransmitter systems, such as dopamine, in strain-dependent effects of anandamide in memory consolidation is discussed.