Morphine sensitization and state-dependent learning in mice



In the present study, the effects of morphine sensitization on morphine-induced impairment of memory formation and the state-dependent retrieval of a passive avoidance task learned under morphine influence have been investigated in mice. Pre-training administration of morphine (0.5, 2.5 and 5 mg/kg) dose dependently suppressed the learning of one-trial passive avoidance task. Pre-test administration of morphine (0.5, 2.5 and 5 mg/kg) induced state-dependent retrieval of the memory acquired under pre-training morphine influence which these effects of morphine is named state-dependent learning. The inhibitory effect of morphine (5 mg/kg) on memory formation was significantly antagonized by pretreatment administration of naloxone (0.025, 0.5 and 1 mg/kg) before the pre-training morphine. The pre-test administration of naloxone dose dependently inhibited the restoration induced by morphine (5 mg/kg). Amnesia induced by pre-training morphine significantly inhibited in morphine-sensitized mice, which had previously received once daily injections of morphine (20 and 30 mg/kg, s.c.) for 3 days. Morphine sensitization did not affect on morphine state-dependent memory of passive avoidance. The inhibition of morphine-induced amnesia in morphine-sensitized mice suppressed by once daily injections of naloxone (0.5, 1 and 2 mg/kg) 30 min prior to s.c. injection of morphine (20 mg/kg/day for 3 days). These results suggest that morphine sensitization affect the impairment of memory formation, but not the facilitation of retrieval induced by morphine.