Reversal of morphine-induced memory impairment in mice by withdrawal in Morris water maze - Possible involvement of cholinergic system

The effects of morphine and morphine withdrawal on memory performance were examined in mice by using Morris water maze task. Morphine-induced memory i mpairment at the doses of 5 and 10 mg/kg recovered after repeated administr ation Oxotremorine, a muscarinic receptor agonist, at the dose of 0.1 mg/kg ip, and physostigmine, a cholinesterase inhibitor, at the dose of 0.1 mg/k g ip, significantly antagonized morphine (10 mg/kg sc)-induced memory impai rment in mice. Furthermore, repeated naloxone (0.5 mg/kg ip) attenuated sco polamiue (0.2 mg/kg ip)-induced memory impairment. By using escalating dose s of morphine for 13 days, morphine-induced memory impairment was continuou sly maintained. When withdrawal was precipitated by naloxone (5 mg/kg ip), or administration of oxotremorine (0.1 and 0.2 mg/kg ip) or physostigmine ( 0.05 and 0.1 mg/kg ip), the impairment was completely reversed. These resul ts suggest that morphine-induced memory impairment could he partially due t o the inhibition of the central cholinergic activity. (C) 2001 Elsevier Sci ence Inc. All rights reserved.