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The Effects of the Monoamine Stabilizer (-)-OSU6162 on Binge-Like Eating and Cue-Controlled Food-Seeking Behavior in Rats
Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm Hlth Care Serv, Stockholm, Sweden..
Univ Cambridge, Dept Psychol, Cambridge, England.;Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge, England..
Univ Cambridge, Dept Psychol, Cambridge, England.;Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge, England..
Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm Hlth Care Serv, Stockholm, Sweden..
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2018 (English)In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 43, no 3, p. 617-626Article in journal (Refereed) Published
Abstract [en]

Binge-eating disorder (BED) is characterized by recurring episodes of excessive consumption of palatable food and an increased sensitivity to food cues. Patients with BED display an addiction-like symptomatology and the dopamine system might be a potential treatment target. The clinically safe monoamine stabilizer (-)-OSU6162 (OSU6162) restores dopaminergic dysfunction in long-term alcohol-drinking rats and shows promise as a novel treatment for alcohol use disorder. Here, the effects of OSU6162 on consummatory (binge-like eating) and appetitive (cue-controlled seeking) behavior motivated by chocolate-flavored sucrose pellets were evaluated in non-food-restricted male Lister Hooded rats. OSU6162 significantly reduced binge-like intake of chocolate-flavored sucrose pellets without affecting prior chow intake. Furthermore, OSU6162 significantly reduced the cue-controlled seeking of chocolate-flavored sucrose pellets under a second-order schedule of reinforcement before, but not after, the delivery and ingestion of reward, indicating a selective effect on incentive motivational processes. In contrast, the dopamine D2/D3 receptor antagonist raclopride reduced the seeking of chocolate-flavored sucrose pellets both pre-and post reward ingestion and also reduced responding under simpler schedules of seeking behavior. The D1/5 receptor antagonist SCH23390 had no effect on instrumental behavior under any reinforcement schedule tested. Finally, local administration of OSU6162 into the nucleus accumbens core, but not dorsolateral striatum, selectively reduced cue-controlled sucrose seeking. In conclusion, the present results show that OSU6162 reduces binge-like eating behavior and attenuates the impact of cues on seeking of palatable food. This indicates that OSU6162 might serve as a novel BED medication.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2018. Vol. 43, no 3, p. 617-626
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Basic Medicine
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URN: urn:nbn:se:uu:diva-341560DOI: 10.1038/npp.2017.215ISI: 000419961500018PubMedID: 28895569OAI: oai:DiVA.org:uu-341560DiVA, id: diva2:1182626
Funder
Swedish Society of Medicine, SLS-253061Wellcome trustSwedish Research Council, 350-2012-230, 2015-03525Swedish Society for Medical Research (SSMF)Available from: 2018-02-14 Created: 2018-02-14 Last updated: 2018-02-14Bibliographically approved

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