Enhancing effects of morphine on methamphetamine-induced reinforcing behavior and its association with dopamine release and metabolism in mice.
Polydrug abuse has become a significant problem worldwide, and the combined use of methamphetamine (MA) and morphine (M) is now highly prevalent among addicts. In the present study, we investigated the neurobehavioral effects of repeated treatment regimens of these drugs (i.p. administration of 0.75 mg/kg/day MA, 5 mg/kg/day M, and their combination for five consecutive days followed by once weekly for five consecutive weeks) in mice. In addition, we used an in vivo microdialysis technique to study the changes in extracellular concentrations of dopamine (DA) and its metabolites in the mouse striatum after challenge administration of these drugs. The results showed that systemic M increased MA-induced conditioned place preference (CPP), as revealed by higher CPP values which were also maintained for a longer duration compared with those induced by an identical dose of MA or M alone. Subsequent to challenge with combined MA and M, mice exhibited an increase in stereotyped behavior, which appeared to be associated with an elevation of extracellular concentration of DA in the striatum. Our findings suggest that M not only produces synergistic effects on MA-induced CPP, but also interacts with MA to induce stereotyped behavioral sensitization which is mediated by an increase in DA outflow in the striatum. These findings provide insight into the behavioral and neurochemical basis responsible for the combined abuse liability of MA and M.
Lan
Kuo-Cheng
KC
Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Chang
Alice Chien
AC
Liu
Shing-Hwa
SH
Ho
Ing Kang
IK
Lin-Shiau
Shoei-Yn
SY
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004357:Drug Synergism; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D051379:Mice; D009020:Morphine / Q000008:administration & dosage*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D012055:Reinforcement Schedule; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology
D008694:Methamphetamine; D009020:Morphine; D004298:Dopamine