Cannabinoid receptor-1 signaling contributions to sign-tracking and conditioned reinforcement in rats

Psychopharmacology (Berl). 2018 Oct;235(10):3031-3043. doi: 10.1007/s00213-018-4993-6. Epub 2018 Aug 14.


Rationale: Endocannabinoids (eCBs) are critical gatekeepers of dopaminergic signaling, and disrupting cannabinoid receptor-1 (CB1) signaling alters DA dynamics to attenuate cue-motivated behaviors. Prior studies suggest that dopamine (DA) release plays a critical role in driving sign-tracking.

Objectives: Here, we determine whether systemic injections of rimonabant, a CB1 receptor inverse agonist, during Pavlovian lever autoshaping impair the expression of sign-tracking. We next examine whether rimonabant blocks the reinforcing properties of the Pavlovian lever cue in a conditioned reinforcement test.

Methods: In Exp. 1, we trained rats in Pavlovian lever autoshaping prior to systemic rimonabant injections (0, 1, 3 mg/kg) during early and late Pavlovian lever autoshaping sessions. In Exp. 2, we trained rats in Pavlovian lever autoshaping prior to systemic rimonabant injections (0, 1 mg/kg) during a conditioned reinforcement test.

Results: Rimonabant dose-dependently decreased lever contact and probability, and increased sign-tracker's latency to approach the lever cue early in Pavlovian training. With extended training, many previously goal-tracking and intermediate rats shifted to lever approach, which remained dose-dependently sensitive to rimonabant. Rimonabant attenuated cue-evoked food cup approach early, but not late, in conditioning, and did not affect pellet retrieval or consumption. The inserted lever cue served as a robust conditioned reinforcer after Pavlovian lever autoshaping, and 1 mg/kg rimonabant blocked conditioned reinforcement.

Conclusions: Together, our results suggest that CB1 signaling mediates two critical properties of incentive stimuli; their ability to attract (Exp. 1) and their ability to reinforce (Exp. 2) behavior.

Keywords: Appetitive; Approach; CB1 receptor; Conditioned reinforcement; Cue-motivated; Endocannabinoids; Incentive; Pavlovian; Sign-tracking.

MeSH terms

  • Animals
  • Conditioning, Classical / drug effects*
  • Conditioning, Classical / physiology
  • Cues
  • Feeding Behavior / drug effects*
  • Feeding Behavior / physiology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB1 / agonists*
  • Reinforcement, Psychology*
  • Rimonabant / pharmacology*
  • Signal Transduction / drug effects*


  • Receptor, Cannabinoid, CB1
  • Rimonabant