Effects of the cannabinoid CB(1) receptor antagonist, SR141716A, after Delta(9)-tetrahydrocannabinol withdrawal

Eur J Pharmacol. 2000 Jan 3;387(1):47-53. doi: 10.1016/s0014-2999(99)00792-x.

Abstract

Rats were trained to lever press according to variable interval 10 s schedules during daily experimental sessions composed of six 3 min food reinforcement periods and were treated twice daily for 6 days with either vehicle or escalating regimens of Delta(9)-tetrahydrocannabinol. On days 7 and 8, the rats were challenged with vehicle and cumulative doses of SR141716A (N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4, -dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxyamide hydrochloride), a cannabinoid CB(1) receptor antagonist, up to 3 and 9 mg/kg, respectively. Response rates increased during Delta(9)-tetrahydrocannabinol withdrawal and towards those of the vehicle treatment group suggesting a waning of the direct effects of Delta(9)-tetrahydrocannabinol. SR141716A reduced response rates but only in rats pre-treated with Delta(9)-tetrahydrocannabinol. These data suggest that dependence upon Delta(9)-tetrahydrocannabinol was induced and SR141716A precipitated withdrawal.

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Dronabinol / pharmacology*
  • Male
  • Piperidines / pharmacology*
  • Psychotropic Drugs / adverse effects*
  • Pyrazoles / pharmacology*
  • Rats
  • Rats, Long-Evans
  • Receptors, Cannabinoid
  • Receptors, Drug / antagonists & inhibitors*
  • Rimonabant
  • Substance Withdrawal Syndrome / etiology*
  • Substance Withdrawal Syndrome / prevention & control
  • Substance-Related Disorders / etiology
  • Substance-Related Disorders / prevention & control

Substances

  • Piperidines
  • Psychotropic Drugs
  • Pyrazoles
  • Receptors, Cannabinoid
  • Receptors, Drug
  • Dronabinol
  • Rimonabant