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.