Chronic WIN55,212-2 elicits sustained and conditioned increases in intracranial self-stimulation thresholds in the rat

Behav Brain Res. 2010 May 1;209(1):114-8. doi: 10.1016/j.bbr.2010.01.024. Epub 2010 Jan 25.

Abstract

The present study sought to examine whether repeated administration of the CB(1) receptor agonist WIN55,212-2 affected intracranial self-stimulation (ICSS) behavior and induced phenomena of tolerance or sensitization, similar to typical addictive drugs. Rats received intraperitoneal injections of vehicle for 5 days, vehicle or WIN55,212-2 (0.1, 0.3 or 1mg/kg) for 20 subsequent days, and vehicle for 5 additional days. Thresholds for ICSS were measured before and after each injection. The initial five injections of vehicle did not affect ICSS thresholds. WIN55,212-2 (1mg/kg) significantly increased ICSS thresholds from the first day of administration, an effect that remained stable across the subsequent days of administration. During the 5 additional days, where WIN55,212-2 was substituted with vehicle, rats demonstrated a conditioned increase in postinjection thresholds that was significant the first 3 days of this period. These findings indicate that repeated WIN55,212-2 administration elicited a sustained increase in ICSS, i.e., phenomena of tolerance or sensitization were not observed. The present data demonstrate cannabinoid-predictive stimuli that may gain affective salience and play an important role in maintaining cannabinoid administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects
  • Benzoxazines / pharmacology*
  • Biophysics / methods
  • Calcium Channel Blockers / pharmacology*
  • Conditioning, Operant / drug effects*
  • Electric Stimulation / methods
  • Male
  • Medial Forebrain Bundle / physiology
  • Morpholines / pharmacology*
  • Naphthalenes / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Self Stimulation / drug effects*
  • Self Stimulation / physiology*
  • Sensory Thresholds / drug effects

Substances

  • Benzoxazines
  • Calcium Channel Blockers
  • Morpholines
  • Naphthalenes
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone