Cannabinoid receptor-1 signaling contributions to sign-tracking and conditioned reinforcement in rats.
Autor: | Bacharach SZ; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn Street - HSFII Room S263, Baltimore, MD, 21201, USA.; Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD, USA., Nasser HM; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn Street - HSFII Room S263, Baltimore, MD, 21201, USA., Zlebnik NE; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn Street - HSFII Room S263, Baltimore, MD, 21201, USA., Dantrassy HM; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn Street - HSFII Room S263, Baltimore, MD, 21201, USA., Kochli DE; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn Street - HSFII Room S263, Baltimore, MD, 21201, USA., Gyawali U; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn Street - HSFII Room S263, Baltimore, MD, 21201, USA.; Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD, USA., Cheer JF; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn Street - HSFII Room S263, Baltimore, MD, 21201, USA.; Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD, USA.; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA., Calu DJ; 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.; Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD, USA. dcalu@som.umaryland.edu. |
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Jazyk: | angličtina |
Zdroj: | Psychopharmacology [Psychopharmacology (Berl)] 2018 Oct; Vol. 235 (10), pp. 3031-3043. Date of Electronic Publication: 2018 Aug 14. |
DOI: | 10.1007/s00213-018-4993-6 |
Abstrakt: | 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. |
Databáze: | MEDLINE |
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