Responses to drugs of abuse and non-drug rewards in leptin deficient ob/ob mice.

Autor: Muelbl MJ; Neuroscience Research Center and Department of Pharmacology & Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA., Nawarawong NN; Neuroscience Research Center and Department of Pharmacology & Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA., Clancy PT; Neuroscience Research Center and Department of Pharmacology & Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA., Nettesheim CE; Neuroscience Research Center and Department of Pharmacology & Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA., Lim YW; Neuroscience Research Center and Department of Pharmacology & Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA., Olsen CM; Neuroscience Research Center and Department of Pharmacology & Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA. colsen@mcw.edu.
Jazyk: angličtina
Zdroj: Psychopharmacology [Psychopharmacology (Berl)] 2016 Jul; Vol. 233 (14), pp. 2799-811. Date of Electronic Publication: 2016 Jun 03.
DOI: 10.1007/s00213-016-4323-9
Abstrakt: Rationale: Although leptin receptors are found in hypothalamic nuclei classically associated with homeostatic feeding mechanisms, they are also present in brain regions known to regulate hedonic-based feeding, natural reward processing, and responses to drugs of abuse. The ob/ob mouse is deficient in leptin signaling, and previous work has found altered mesolimbic dopamine signaling and sensitivity to the locomotor activating effects of amphetamine in these mice.
Objectives: We directly assessed responses to three drugs of abuse and non-drug rewards in the leptin-deficient ob/ob mouse.
Methods: Ob/ob mice were tested in assays of sweet preference, novelty seeking, and drug reward/reinforcement.
Results: In assays of novelty seeking, novel open field activity and operant sensation seeking were reduced in ob/ob mice, although novel object interaction and novel environment preference were comparable to wild types. We also found that ob/ob mice had specific phenotypes in regard to cocaine: conditioned place preference for 2.5 mg/kg was increased, while the locomotor response to 10 mg/kg was reduced, and cocaine self-administration was the same as wild types. Ob/ob mice also acquired self-administration of the potent opioid remifentanil, but breakpoints for the drug were significantly reduced. Finally, we found significant differences in ethanol drinking in ob/ob mice that correlated negatively with body weight and positively with operant sensation seeking.
Conclusions: In conclusion, ob/ob mice displayed task-specific deficits in novelty seeking and dissociable differences in reward/reinforcement associated with cocaine, remifentanil, and ethanol.
Competing Interests: The authors have no conflicts of interest to report.
Databáze: MEDLINE
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