The influence of central administration of dopaminergic and cholinergic agents on morphine-induced amnesia in morphine-sensitized mice.

In the present study, effects of intracerebroventricular (i.c.v.) injections of dopaminergic and cholinergic agents on morphine-induced amnesia in morphine-sensitized mice were investigated by using a one-trial passive avoidance task. Amnesia induced by pre-training morphine was significantly reversed in morphine-sensitized mice, which had previously received once daily injections of morphine (20 and 30 mg/kg, s.c.) for 3 days. Three daily injections of SKF 38393 (1, 2 and 4 g/mouse, i.c.v.) or SCH 23390 (0.25, 0.5, 0.75 and 1 g/mouse, i.c.v.) before morphine, and during morphine-sensitization, decreased and increased the amnesia induced by pre-training morphine respectively. Three daily injections of quinpirole (0.3, 1 and 3 g/mouse, i.c.v.) or sulpiride (0.03, 0.1, 0.3 and 1 g/mouse, i.c.v.) before morphine, also decreased and increased the amnesia induced by pre-training morphine respectively. Morphine-sensitized mice received similar injections of cholinergic agents. Three daily injections of physostigmine (1, 3 and 5 g/mouse, i.c.v.) or atropine (1, 4 and 7 g/mouse, i.c.v.) before morphine, and during morphine-sensitization, decreased and increased the amnesia induced by pre-training morphine respectively. Three daily injections of nicotine (0.75, 1 and 2 g/mouse, i.c.v.) or mecamylamine (1, 3 and 6 g/mouse, i.c.v.) before morphine, also decreased and increased the amnesia induced by pre-training morphine respectively. The results suggest that morphine sensitization affects the impairment of memory formation and thus it is postulated that central dopaminergic and cholinergic systems may play an important role in this effect.