Dopaminergic-cholinergic interactions in naloxone-induced circling in morphine-dependent rats with nigral lesions

Edgar T. Iwamoto, H. H. Loh, E. Leong Way

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

3-4 weeks after placement of a unilateral, electrolytic lesion of the substantia nigra zona compacta, rats were highly dependent on morphine by the s.c. morphine pellet implantation technique. Following challenge with a supramaximal naloxone dose of 20 mg/kg i.p., both continous contralateral circling behavior and severe withdrawal signs in morphine-dependent, lesioned rats were elicited. After various drug pretreatments, the contralateral circling behavior precipitated by naloxone was: (a) reversed to ipsilateral circling by i.p. apomorphine or d-amphetamine, (b) unaltered by i.p. haloperidol or intraneostriatal arecoline administered into the intact neostriatum, and (c) reversed to ipsilateral circling by the administration of atropine into the intact neostriatum. Atropine, apomorphine and amphetamine all interfered with the manifestation of naloxone-precipitated abstinence. These data suggest that a diminution of dopaminergic or an enhancement of cholinergic activities, or both, occur at the level of the neostriatum during naloxone-precipitated withdrawal in morphine-dependent rats.

Original languageEnglish (US)
Pages (from-to)39-54
Number of pages16
JournalEuropean Journal of Pharmacology
Volume38
Issue number1
DOIs
StatePublished - Jul 1976

Bibliographical note

Funding Information:
This work was supported in part by research grants from the National Institute of Drug Abuse DA 00037 and DA 00564. Portions of this paper were presented at the 58th Annual Meeting of the Federation of American Societies for Experimental Biology (FAS-EB), Atlantic City, N.J., April 7--12, 1974 and at the Western Pharmacology Society Meetings, Honolulu, Hawaii, January 1975.

Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.

Keywords

  • ACh agonists
  • ACh antagonists
  • Circling behavior
  • DA agonists
  • DA antagonists
  • Electrolytic SNC lesions
  • Morphine-dependent rats
  • Naloxone-precipitated withdrawal

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