Anandamide and memory in CD1 mice: effects of immobilization stress and of prior experience

Five sets of experiments were carried out with CD1 mice tested in a one-trial inhibitory avoidance task. In a first set, immediately posttraining administrations of the endogenous ligand for the cannabinoid CB1 receptor anandamide (arachidonylethanolamide) (3 or 6 mg/kg) dose-dependently impaired memory consolidation in mice. A lower dose (1.5 mg/kg) was ineffective. In a second set of experiments, which was carried out at the same time of the first set, preexposure of the animals to the testing apparatus decreased the effect of the drug, as compared with non-preexposed mice. In a third set of experiments, administration of anandamide (3 or 6 mg/kg) prior to the retention test did not affect the retention performance of mice given posttraining injections of either saline or anandamide. These findings indicate that the memory-impairing effects of posttraining administration of anandamide are not state-dependent. In the fourth and fifth series of experiments, carried out with non-preexposed mice, an otherwise ineffective immobilization stress (15 min) enhanced the memory-impairing effect of anandamide, and an otherwise ineffective dose of naltrexone (0.1 mg/kg) completely antagonized the effect. The results are discussed in terms of attenuation of emotionality, resulting in impaired retention, following anandamide administration, and of involvement of opioid system in the effect of this drug.