α7 Nicotinic acetylcholine receptors in the central amygdaloid nucleus alter naloxone-induced withdrawal following a single exposure to morphine

Shigeru Ishida, Yoichi Kawasaki, Hiroaki Araki, Masato Asanuma, Hisashi Matsunaga, Toshiaki Sendo, Hiromu Kawasaki, Yutaka Gomita, Yoshihisa Kitamura

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Rationale: Negative motivational withdrawal from acute opiate dependence was induced by an opioid antagonist, and the withdrawal signs prevented by pretreatment with nicotine. Objectives: The present study was undertaken to examine the mechanism of nicotine-induced attenuation of withdrawal precipitated by naloxone in rats administered a single dose of morphine. Methods: Conditioned place aversion (CPA) was precipitated by naloxone in rats exposed once to morphine. Nicotinic acetylcholine receptor (nAChR) agonists were microinjected into the central amygdaloid nucleus (CeA) before naloxone was administered. Additionally, c-Fos expression in the amygdala was measured in rats exposed to α7 nAChR ligands. Results: The microinjection of nicotine (0.3 and 1.0 μg/μl) into the CeA dose-dependently inhibited naloxone-induced CPA. This inhibition of CPA was reversed by methyllycaconitine (MLA), an α7 nAChR antagonist. CPA was also significantly attenuated by the microinjection of tropisetron (3.0 μg/μl), an α7 nAChR agonist and 5-hydroxytriptamine 3 (5-HT3) receptor antagonist, but not by ondansetron (1.0 and 3.0 μg/μl), a 5-HT3 receptor antagonist. The microinjection of PNU-282987 (3.0 μg/μl), a selective α7 nAChR agonist, into the CeA also inhibited CPA. Furthermore, nicotine increased c-Fos expression in the CeA, but not the medial or basolateral amygdaloid nucleus. The increase of c-Fos in the CeA was significantly inhibited by MLA. Conclusion: Nicotine-induced attenuation of CPA precipitated by naloxone is mediated by the α7 nAChR subtype, and the CeA is one of the regions of the brain involved in the effect of nicotine on acutely opiate-dependent subjects.

Original languageEnglish
Pages (from-to)923-931
Number of pages9
JournalPsychopharmacology
Volume214
Issue number4
DOIs
Publication statusPublished - Apr 1 2011

Keywords

  • Acute opiate dependence
  • Central amygdaloid nucleus
  • Microinjection
  • Nicotine
  • c-Fos
  • α7 nicotinic acetylcholine receptor

ASJC Scopus subject areas

  • Pharmacology

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