Involvement of the amygdala on place aversion induced by naloxone in single-dose morphine-treated rats

Shigeru Ishida, Riho Shimosaka, Yoichi Kawasaki, Chunyu Jin, Yoshihisa Kitamura, Hiroaki Araki, Toshiaki Sendo, Yutaka Gomita

Research output: Contribution to journalReview articlepeer-review

11 Citations (Scopus)


Signs characteristic of opiate withdrawal symptoms can be precipitated by an opiate antagonist after short-term infusion or even a single dose of an opiate both in humans and in animals. This phenomenon has been referred to as acute dependence. In contrast to extensive studies on chronic dependence, less is known about the neural mechanisms mediating acute dependence. It will benefit the development of appropriate therapies to facilitate opiate abstinence and reduced craving to better understand the mechanisms underlying acute opiate dependence and to determine whether there are dissociation and similarity between the early and fully developed stages of dependence. In the present study, we examined the influence of c-Fos expression in the amygdala in acquisition of conditioned place aversion (CPA) induced by naloxone-precipitated withdrawal from a single morphine exposure 24 h earlier. The effect of microinjection into the central amygdaloid nucleus (CeA) of various kinds of glutamatergic neurotransmission inhibitors was also investigated. Findings showed that CeA displayed significant increase in c-Fos expression in the acquisition of CPA. Furthermore, CPA was attenuated significantly and dose-dependently by microinjection into CeA of all glutamatergic neurotransmission inhibitors (NMDA receptor antagonist (+)-5-methyl-10,11- dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine maleate (MK-801), AMPA receptor antagonist 1-(4-aminophenyl)4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI52466), metabotropic glutamate receptor antagonist (±)-α-methyl-4-carboxyphenylglycine (MCPG), and glutamate release inhibitor riluzole). These findings suggest that CeA involves the acquisition of CPA induced by naloxone-precipitated withdrawal from a single morphine exposure, and the function of the glutamatergic system projected from the amygdala to nucleus accumbens plays a facilitative role in formation of morphine dependence.

Original languageEnglish
Pages (from-to)395-403
Number of pages9
JournalYakugaku Zasshi
Issue number3
Publication statusPublished - Mar 2008


  • Acute dependence
  • Central amygdaloid nucleus (CeA)
  • Conditioned place aversion
  • Glutamatergic neurotransmission
  • Morphine
  • Naloxone

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science


Dive into the research topics of 'Involvement of the amygdala on place aversion induced by naloxone in single-dose morphine-treated rats'. Together they form a unique fingerprint.

Cite this