Possible interaction between central cholinergic muscarinic and opioid peptidergic systems during memory consolidation in mice.

Naloxone (0.01-1.00 mg/kg, ip) facilitated retention of a one-trial inhibitory avoidance task, when administered to male Rockland mice immediately after training, as indicated by performance on a retention test 48 hr later. The dose-response curve was an inverted U in this range of dose. In these conditions naloxone did not lengthen latencies to step-through during the retest of unshocked mice. Higher doses of naloxone (3.00 and 10.00 mg/kg, ip) tended to increase latencies to step-through of both shocked and unshocked mice. These facts rule out an aversive effect of naloxone for low and moderate doses but not for high doses. The influence of naloxone (0.10 mg/kg, ip) on retention was time dependent, which suggests that naloxone facilitated memory consolidation processes. The effects of naloxone were prevented by morphine in both an amnesic and a nonamnesic dose (1.0 and 0.5 mg/kg, ip, respectively). Therefore, naloxone probably facilitated retention as a function of its opiate antagonist properties. The memory facilitation induced by naloxone (0.10 mg/kg, ip) was antagonized by atropine (0.5 mg/kg, ip) but not by methylatropine (0.5 mg/kg, ip), mecamilamine (5 mg/kg, ip), or hexametonium (5 mg/kg, ip). Further, there was a mutual potentiation for both naloxone (0.01 mg/kg, ip) and the muscarinic agonist oxotremorine (6.25 and 12.5 micrograms/kg, ip) administered simultaneously, in doses which had no effect on their own. Moreover, an amnesic dose of atropine (10.00 mg/kg, ip) prevented the enhancement of retention induced by naloxone, while an amnesic dose of morphine (1.00 mg/kg, ip) did not modify the facilitatory effect of oxotremorine (50 micrograms/kg, ip) on retention. An inhibitory modulatory role for endogenous opioid systems on the activity of central cholinergic muscarinic systems during memory consolidation is suggested.