title: Relapse of methamphetamine-seeking behavior in C57BL/6J mice demonstrated by a reinstatement procedure involving intravenous self-administration.
abstract: There is an urgent need to develop a reliable mouse model of relapse to address the genetic factors involved in susceptibility to relapse of drug-seeking behavior by using mutant mice. This paper presents a feasible way to reinstate extinguished methamphetamine (METH)-seeking behavior. Male C57BL/6J mice acquired stable nose-poking responses for taking METH after approximately 10 daily 3-h sessions of METH (0.1mg/kg/infusion) self-administration under a fixed ratio 1 or 2 (FR1/2) schedule. During the self-administration, cue- and hole-lamps indicated the availability of METH and were inactivated simultaneously with each infusion for 5s. The mice were exposed to extinction training in the absence of METH-paired stimuli (cue- and hole-lamps) and METH infusion, until they met the extinction criterion (less than 25 active responses or 30% of active responses in the stable self-administration phase on 2 consecutive days). METH-paired stimuli (cue- and hole-lamps) during METH self-administration reliably triggered a relapse of METH-seeking behavior in the absence of METH infusion. A combination of non-contingent intravenous (i.v.) priming and self-injected METH also increased the reinstatement of METH-seeking behavior in the absence of METH-paired stimuli (cue- and hole-lamps) and without METH infusion posterior to the self-injection. These results suggest that the mouse model of relapse in our study might provide a new stage for the exploration of genetic factors involved in relapse of drug dependence and of the underlying mechanisms of drugs of abuse.
authors.affiliation: Department of Neuropsychopharmacology & Hospital Pharmacy, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8560, Japan.
authors.forename: Yijin
authors.initials: Y
authors.lastname: Yan
authors.forename: Atsumi
authors.initials: A
authors.lastname: Nitta
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizoguchi
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamada
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nabeshima
mesh_terms: D019969:Amphetamine-Related Disorders / Q000523:psychology*; D000818:Animals; D002406:Catheterization, Peripheral; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003463:Cues; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012646:Self Administration; D015819:Substance Abuse, Intravenous / Q000523:psychology*
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine