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

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

Author information

1
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn Street - HSFII Room S263, Baltimore, MD, 21201, USA.
2
Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD, USA.
3
Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
4
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn Street - HSFII Room S263, Baltimore, MD, 21201, USA. dcalu@som.umaryland.edu.
5
Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD, USA. dcalu@som.umaryland.edu.

Abstract

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

PMID:
30109373
DOI:
10.1007/s00213-018-4993-6

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