The effect of AM281, a cannabinoid antagonist, on memory performance during spontaneous morphine withdrawal in mice
نویسندگان
چکیده
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.
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AM281, Cannabinoid Antagonist/Inverse agonist, Ameliorates Scopolamine-Induced Cognitive Deficit
Objective(s) Cannabinoids have been implicated in memory deficit. We examined the effect of AM281, cannabinoid antagonist/inverse agonist in prevention of scopolamine-induced cognitive deficit. Materials and Methods Object recognition task was used to evaluate memory in mice. Exploration time in the first and the second trial was recorded. The differences in exploration between a previously...
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