Behavioral mechanisms underlying inhibition of food-maintained responding by the cannabinoid receptor antagonist/inverse agonist SR141716A

Eur J Pharmacol. 2004 Jan 1;483(1):55-63. doi: 10.1016/j.ejphar.2003.10.012.

Abstract

This study investigated the possible behavioral mechanisms underlying the anorectic effect of the cannabinoid CB(1) receptor antagonist/inverse agonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR141716A). Male or female rats were food-restricted and trained to emit stable responding in daily 10-min, fixed ratio 10 food-reinforced operant sessions. Under these conditions, as well as under free-feeding conditions, SR141716A inhibited food-maintained responding (ED(50) values ranging from 0.92 to 2.52 mg/kg, i.p.). In the same operant procedure, SR141716A suppressed intracranial self-stimulation with a potency which was slightly lower than the anorectic potency (ED(50): 4.50 mg/kg). As assessed during a 10-min test period SR141716A (1-10 mg/kg) did not affect activity counts; suggesting that the observed inhibition of operant behavior is not a direct consequence of impairment of locomotor activity. SR141716A, however, attenuated saccharin-preference in a conditioned taste aversion paradigm (ED(50): 6.45 mg/kg). Although the data support the suggestion that the anorectic effect of SR141716A results from an attenuating effect on the rewarding effect of food, the contribution of drug-induced aversion/malaise cannot be excluded.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Cannabinoid Receptor Agonists*
  • Cannabinoid Receptor Antagonists*
  • Conditioning, Operant / drug effects*
  • Dose-Response Relationship, Drug
  • Eating / drug effects
  • Female
  • Food
  • Male
  • Motor Activity / drug effects
  • Piperidines / pharmacology*
  • Pyrazoles / pharmacology*
  • Rats
  • Rats, Wistar
  • Rimonabant
  • Self Stimulation
  • Taste / drug effects

Substances

  • Cannabinoid Receptor Agonists
  • Cannabinoid Receptor Antagonists
  • Piperidines
  • Pyrazoles
  • Rimonabant