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Pharmacol Biochem Behav. 2008 May;89(3):374-83. doi: 10.1016/j.pbb.2008.01.012. Epub 2008 Jan 26.

Different time schedules affect conditioned place preference after morphine and morphine-6-glucuronide administration.

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Norwegian Institute of Public Health, Division of Forensic Toxicology and Drug Abuse, Nydalen, Oslo, Norway.


A number of studies have investigated the reward potential of morphine, using the Conditioned Place Preference (CPP) procedure. The morphine-metabolite morphine-6-glucuronide (M6G) is known to have analgesic activity comparable to morphine, but its reward properties are unclear. An unbiased two compartment counterbalanced procedure was used to investigate the induction of CPP by morphine or M6G in C57BL/6J-Bom mice using different conditioning schedules. The conditioning sessions took place either immediately after the injections and lasted either 20 or 40 min, or were delayed until 15 min after the injections and lasted for 20 min. Locomotor activity was recorded during the conditioning sessions. Morphine induced CPP when the 20-minute conditioning sessions were conducted directly after the injections, but not when they were delayed. M6G induced CPP when the 20-minute conditioning sessions were delayed, but not when the animals were conditioned directly after the injections. Neither morphine nor M6G induced CPP after 40-minute direct conditioning sessions. M6G had a biphasic effect on locomotor activity, with an initial decrease followed by excitation. This study indicates that M6G has rewarding effects, and might contribute to the development of addiction after heroin or morphine administration. However, in any attempts to explore the reward properties of M6G, the choice of time schedule should be carefully considered.

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