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Subchronic cannabinoid agonist (WIN 55,212-2) treatment during cocaine abstinence alters subsequent cocaine seeking behavior

Academic Article
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Overview

authors

  • Gonzalez-Cuevas, G.
  • Aujla, H.
  • Martin-Fardon, Remi
  • Lopez-Moreno, J. A.
  • Navarro, M.
  • Weiss, Friedbert

publication date

  • November 2007

journal

  • Neuropsychopharmacology  Journal

abstract

  • The co-abuse of marijuana with cocaine is widespread, but it has not been until recently that the relationship between the behavioral effects of cannabinoids and cocaine has begun to be unveiled in animal models. Male Wistar rats were trained to intravenously self-administer cocaine until a stable baseline was reached. Rats then were subjected to a 5-day cocaine deprivation period during which they were treated daily with the cannabinoid receptor agonist WIN 55,212-2 (R-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate) (0, 0.3, 1, and 3 mg/kg; i.p.). Following this subchronic treatment, rats were tested, in counterbalanced order, in a test of anxiety (elevated plus-maze), as well as extinction and cue-induced reinstatement tests, the latter conducted according to a between-within procedure. Subchronic administration of WIN 55,212-2 was found to produce dose-dependent alterations of performance in the extinction, reinstatement, and anxiety tests with the lowest dose of WIN 55,212-2 producing the highest resistance to extinction and reinstatement, and the highest dose of WIN 55,212-2 producing the highest anxiolytic activity. Subchronic treatment with WIN 55,212-2 in rats without a history of cocaine self-administration did not affect anxiety levels. The results suggest an important role of the cannabinoid system in neuronal processes underlying cocaine seeking behavior. However, further studies will be necessary to understand possible implications of these findings for a role of the cannabinoid system as a treatment target for human cocaine abuse.

subject areas

  • Analgesics
  • Animals
  • Behavior, Animal
  • Benzoxazines
  • Cocaine
  • Conditioning, Operant
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Extinction, Psychological
  • Male
  • Maze Learning
  • Morpholines
  • Naphthalenes
  • Rats
  • Rats, Wistar
  • Self Administration
  • Substance Withdrawal Syndrome
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Research

keywords

  • WIN 55,212-2
  • anxiety
  • cannabinoids
  • cocaine
  • extinction
  • reinstatement
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Identity

International Standard Serial Number (ISSN)

  • 0893-133X

Digital Object Identifier (DOI)

  • 10.1038/sj.npp.1301365

PubMed ID

  • 17392740
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Additional Document Info

start page

  • 2260

end page

  • 2266

volume

  • 32

issue

  • 11

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