Long-lasting rewarding effects of morphine induced by drug primings.
To evaluate the persistence of the rewarding effects of morphine, the acquisition, maintenance, extinction and reinstatement of a conditioned place preference (CPP) was assessed in OF1 mice. In Experiment 1, the persistence of morphine-induced CPP was evaluated weekly. Mice showed CPP after four sessions of conditioning with 5, 10, 20 and 40 mg/kg of morphine, which lasted 0, 1, 2 and 4 weeks, respectively. In Experiment 2, after four sessions of conditioning with 40 mg/kg of morphine, the effects of four schedules of extinction differing in the time interval (2, 4, 6 or 8 weeks) between sessions were evaluated. CPP was no longer evident after 8 weeks for the groups examined each 2 or 8 weeks and after 12 weeks for the groups examined each 4 and 6 weeks. After extinction, the reinstating effects of a priming dose of 20 mg/kg of morphine were demonstrated. This procedure of extinction/reinstatement was repeated with a decreasing priming dose of morphine (10, 5, 2.5 and 1.25 mg/kg) until a noneffective dose was found. These results show that morphine-induced CPP is very persistent over time, suggesting that drug exposure induces long-lasting changes in the brain, which supports the idea that drug addiction must be considered as a chronic, lifelong disorder.
Ribeiro Do Couto
B
B
Departamento de Psicobiología, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez, 21 46010 Valencia, Spain.
Aguilar
M A
MA
Rodríguez-Arias
M
M
Miñarro
J
J
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002908:Chronic Disease; D003213:Conditioning, Psychological / Q000187:drug effects; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000503:physiopathology*; D012008:Recurrence; D012201:Reward; D013997:Time Factors
D000701:Analgesics, Opioid; D009020:Morphine