title: Transient drug-primed but persistent cue-induced reinstatement of extinguished methamphetamine-seeking behavior in mice.
abstract: It is essential to develop animal models to study the role of genetic factors in the relapse of drug-seeking behavior in genetically engineered mutant mice. This paper reports a typical model of drug-primed and cue-induced reinstatement of extinguished methamphetamine (METH)-seeking behavior in mice. C57BL/6J mice were trained to self-administer METH (0.1mg/kg/infusion) by poking their nose into an active hole under a fixed ratio schedule in daily 3-h sessions. After acquiring stable METH self-administration behavior, the mice were subjected to extinction training in the absence of both METH and METH-associated cues. Once the active nose-poking responses were extinguished, drug-primed and cue-induced reinstatement were investigated according to a within-subjects design. A priming injection of METH reliably reinstated the extinguished drug-seeking behavior in the absence of both METH and METH-associated cues. Interestingly, the drug-primed METH-seeking behavior disappeared within 2 months after withdrawal from METH, while cue-induced reinstatement of extinguished METH-seeking behavior lasted for at least 5 months after the withdrawal. A correlation study revealed that drug-primed, but not cue-induced, reinstatement behavior was positively correlated with the total amount of METH taken by individuals during METH self-administration. In conclusion, our findings suggest that the present reinstatement procedure for mouse model of relapse is useful and reliable, and different neural mechanisms may be involved in drug-primed and cue-induced METH-seeking behavior.
authors.affiliation: Department of Neuropsychopharmacology & Hospital Pharmacy, Nagoya University, Graduate School of Medicine, Nagoya 466-8560, Japan.
authors.forename: Yijin
authors.initials: Y
authors.lastname: Yan
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamada
authors.forename: Atsumi
authors.initials: A
authors.lastname: Nitta
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nabeshima
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D003463:Cues; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D005108:Extinction, Psychological / Q000187:drug effects*; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration; D019966:Substance-Related Disorders / Q000523:psychology*
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine