The effect of AM281, a cannabinoid antagonist, on memory performance during spontaneous morphine withdrawal in mice

Abrupt cessation of morphine leads to withdrawal signs and cognitive deficits. Endocannabinoid system is activated during withdrawal; therefore, the aim of the present study was to assess the effects of AM281, cannabinoid antagonist/inverse agonist, on memory deficit following spontaneous morphine withdrawal. Cognition was evaluated by using the object recognition task. The novel object recognition task was tested in a square wooden open-field box using objects. The test was consisting of three sections: 15 min exploration, first trial for 12 min and second one for 5 min. In the second trial the difference in exploration between a previously seen object and a novel one, was considered as an index of memory performance (recognition index - RI). Male mice were made dependent by increasing doses of morphine (30-90 mg/kg) subcutaneously twice daily for 3 days. AM281 (0.62, 1.25 and 2.5 mg/kg) were used in chronic form concurrent with morphine i.p. or acutely (2.5, 5 and 10 mg/kg) on the last day. RI was evaluated on the third day 4 h after the last dose of morphine. Chronic administration of AM281 at 2.5 mg/kg improved RI to the 22.1 ± 4.8 and single dose of AM281 at 5 mg/kg improved the memory impairment to the 8.5 ± 4, as compared with vehicle-treated which was 4.8 ± 2.5. The results suggested that administration of AM281 at a dose of 2.5 mg/kg in chronic form and 5 mg/kg in acute dose improved memory.