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 KATP 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 Ag/mouse) reversed the effect of pre-test morphine administration. The KATP channel blocker, glibenclamide (0.1, 0.5 and 1 Ag/mouse), showed effects similar to those of pretest administration of morphine. Glibenclamide tended to potentiate the morphine response. Scopolamine (0.15 and 0.30 Ag/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 Ag/mouse), a KATP 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 KATP channel modulators may be involved, at least in part, in morphine state dependence through a cholinergic system mechanism.
