Influence of central administration ATP-dependent K + channel on morphine state-dependent memory of passive avoidance

Abstract

Pre-training injection of a moderate dose of morphine (5–10 mg/kg) in a step-down passive avoidance task induced state-dependent learning with impaired memory retrieval on the test day. The impairment of memory was restored after the pre-test administration of the same dose of the drug. We have studied the effect of intracerebroventricular administration of naloxone and K ATP channel modulators (glibenclamide and diazoxide) on the test day on restoration of memory by morphine in mice. The effect of scopolamine on restoration of memory on the test-day by glibenclamide was studied as well. Naloxone pretreatment (0.006, 0.025 and 0.1 μg/mouse) reversed the effect of pre-test morphine administration. The K ATP channel blocker, glibenclamide (0.1, 0.5 and 1 μg/mouse), showed effects similar to those of pre-test administration of morphine. Glibenclamide tended to potentiate the morphine response. Scopolamine (0.15 and 0.30 μg/mouse) prevented the effect of glibenclamide on the restoration of memory. The pre-test administration of different doses of diazoxide (1.7, 5 and 15 μg/mouse), a K ATP channel opener, showed no effect on restoration of memory when used alone but decreased morphine state-dependence. Diazoxide blocked the effects of glibenclamide on memory restoration. It is concluded that K ATP channel modulators may be involved, at least in part, in morphine state dependence through a cholinergic system mechanism.