Relapse of methamphetamine-seeking behavior in C57BL/6J mice demonstrated by a reinstatement procedure involving intravenous self-administration

Yijin Yan, Atsumi Nitta, Hiroyuki Mizoguchi, Kiyofumi Yamada, Toshitaka Nabeshima

Research output: Contribution to journalArticle

29 Citations (Scopus)

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 (0.1 mg/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 5 s. 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.

Original languageEnglish
Pages (from-to)137-143
Number of pages7
JournalBehavioural Brain Research
Volume168
Issue number1
DOIs
Publication statusPublished - 15-03-2006
Externally publishedYes

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience

Cite this