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

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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.

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Funding

This work was supported by a McKnight Memory and Cognitive Disorders Award (DJC), a NARSAD Young Investigator Grant No. 24950 (DJC), NIDA grants R01DA043533 (DJC), R01DA042595 (JFC) and R01DA022340 (JFC), and the Department of Anatomy and Neurobiology at the University of Maryland, School of Medicine. The authors declare that they do not have any conflicts of interest (financial or otherwise) related to the data presented in this manuscript.

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Author notes

  1. Sam Z. Bacharach and Helen M. Nasser contributed equally to this work.

Authors and Affiliations

  1. Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn Street – HSFII Room S263, Baltimore, MD, 21201, USA

    Sam Z. Bacharach, Helen M. Nasser, Natalie E. Zlebnik, Hannah M. Dantrassy, Daniel E. Kochli, Utsav Gyawali, Joseph F. Cheer & Donna J. Calu

  2. Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD, USA

    Sam Z. Bacharach, Utsav Gyawali, Joseph F. Cheer & Donna J. Calu

  3. Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA

    Joseph F. Cheer

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  1. Sam Z. Bacharach
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  2. Helen M. Nasser
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  3. Natalie E. Zlebnik
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  4. Hannah M. Dantrassy
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Corresponding author

Correspondence to Donna J. Calu.

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All procedures were performed in accordance with the “Guide for the care and use of laboratory animals” (8th edition, 2011, US National Research Council) and were approved by the University of Maryland, School of Medicine Institutional Animal Care and Use Committee (IACUC).

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Bacharach, S.Z., Nasser, H.M., Zlebnik, N.E. et al. Cannabinoid receptor-1 signaling contributions to sign-tracking and conditioned reinforcement in rats. Psychopharmacology 235, 3031–3043 (2018). https://doi.org/10.1007/s00213-018-4993-6

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