Delta9-tetrahydrocannabinol-induced conditioned place preference and intracerebroventricular self-administration in rats

Eur J Pharmacol. 2004 Dec 3;506(1):63-9. doi: 10.1016/j.ejphar.2004.10.043.


On the basis of contradictory findings on the rewarding effects of Delta9-tetrahydrocannabinol (Delta9-THC) in laboratory animals, the effect of the compound on conditioned place preference and intracerebroventricular (i.c.v.) self-administration in a free-choice procedure, using a wide range of doses (0.015-6 mg/kg for conditioned place preference test and 0.01-1 microg/2 microl/infusion for i.c.v. self-administration), was studied in Wistar rats. The present results showed that Delta9-THC induced reward in both tests, but only at the lowest tested doses (0.075-0.75 mg/kg i.p. for conditioned place preference test and 0.01-0.02 microg/infusion for i.c.v. self-administration). This effect was fully antagonised by i.p. pretreatment with the cannabinoid CB1 receptor antagonist, SR 141716A [N-piperidino-5-(4-chlorophenyl)1-(2,4-dichlorophenyl)-4 methyl pyrazole 3-carboxamide] (0.25-1 mg/kg), and the opiate receptor antagonist, naloxone (0.5-2 mg/kg), suggesting the involvement of both endocannabinoid and opioid systems. In conclusion, these findings demonstrate, for the first time, that low doses of Delta9-THC can act as an effective reinforcer in Wistar rats providing a reliable animal model of human marijuana abuse.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Conditioning, Operant / drug effects*
  • Dose-Response Relationship, Drug
  • Dronabinol / analogs & derivatives
  • Dronabinol / pharmacology*
  • Injections, Intraventricular
  • Male
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Piperidines / pharmacology
  • Psychotropic Drugs / pharmacology
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Wistar
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors
  • Rimonabant
  • Self Administration / methods


  • Narcotic Antagonists
  • Piperidines
  • Psychotropic Drugs
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • Naloxone
  • Dronabinol
  • Rimonabant