Cannabinoid modulation of opiate reinforcement through the ventral striatopallidal pathway

Neuropsychopharmacology. 2006 Apr;31(4):804-13. doi: 10.1038/sj.npp.1300848.


Recent evidence indicates that cannabinoid-1 (CB1) receptors play a role in the mediation of opiate reward, though the neural mechanisms for this process have not been characterized. The present experiments investigated the influence of CB1 receptors in the ventral striatopallidal system on opiate-induced neurochemical events and opiate self-administration behavior in rats. Acute morphine administration (3 mg/kg) significantly reduced ventral pallidal GABA efflux in a manner similar to that produced by heroin self-administration. This neurochemical effect was reversed by doses of the selective CB1 antagonist SR 141716A (Rimonabant; 1 and 3 mg/kg) that also significantly reduce opiate reward. Morphine-induced increases in nucleus accumbens dopamine levels were unaltered by SR 141716A. Intravenous heroin self-administration (0.02 mg/infusion) was significantly reduced by intra-accumbens, but not intraventral pallidal SR 141716A infusions (1 and 3 microg/side), implicating nucleus accumbens CB1 receptors in the modulation of opiate reinforcement. In contrast, SR14716A did not alter cocaine self-administration (0.125 mg/inf), cocaine-induced (10 mg/kg) decrements in ventral pallidal GABA efflux or cocaine-induced increases in accumbens dopamine. This is consistent with evidence that selective inactivation of CB1 receptors reduces opiate-, but not psychostimulant-maintained self-administration. The CB1 receptor agonist WIN 55,212-2 (5 mg/kg) reduced pallidal GABA efflux in a manner similar to morphine, and this effect was reversed by the opiate receptor antagonist naloxone. Collectively these findings suggest that CB1 receptors modulate opiate reward through the ventral striatopallidal projection and that the modulation of this projection system may be involved in the reciprocal behavioral effects between cannabinoids, and opioids.

Publication types

  • Comparative Study

MeSH terms

  • Analgesics, Opioid / administration & dosage*
  • Animals
  • Area Under Curve
  • Behavior, Animal / drug effects
  • Cannabinoids / antagonists & inhibitors
  • Cannabinoids / pharmacology*
  • Cocaine / administration & dosage
  • Conditioning, Operant / drug effects
  • Corpus Striatum / drug effects*
  • Corpus Striatum / physiology
  • Dopamine / metabolism
  • Drug Administration Routes
  • Drug Interactions
  • Male
  • Microdialysis / methods
  • Morphine / administration & dosage*
  • Neural Pathways / drug effects*
  • Piperidines / pharmacology
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Wistar
  • Reinforcement, Psychology*
  • Rimonabant
  • Self Administration / methods
  • Time Factors
  • gamma-Aminobutyric Acid / metabolism


  • Analgesics, Opioid
  • Cannabinoids
  • Piperidines
  • Pyrazoles
  • gamma-Aminobutyric Acid
  • Morphine
  • Cocaine
  • Rimonabant
  • Dopamine