Deficits of mesolimbic dopamine neurotransmission in rat dietary obesity.

Full Abstract

Increased caloric intake in dietary obesity could be driven by central mechanisms that regulate reward-seeking behavior. The mesolimbic dopamine system, and the nucleus accumbens in particular, underlies both food and drug reward. We investigated whether rat dietary obesity is linked to changes in dopaminergic neurotransmission in that region. Sprague-Dawley rats were placed on a cafeteria-style diet to induce obesity or a laboratory chow diet to maintain normal weight gain. Extracellular dopamine levels were measured by in vivo microdialysis. Electrically evoked dopamine release was measured ex vivo in coronal slices of the nucleus accumbens and the dorsal striatum using real-time carbon fiber amperometry. Over 15 weeks, cafeteria-diet fed rats became obese (>20% increase in body weight) and exhibited lower extracellular accumbens dopamine levels than normal weight rats (0.007+/-0.001 vs. 0.023+/-0.002 pmol/sample; P<0.05). Dopamine release in the nucleus accumbens of obese rats was stimulated by a cafeteria-diet challenge, but it remained unresponsive to a laboratory chow meal. Administration of d-amphetamine (1.5 mg/kg i.p.) also revealed an attenuated dopamine response in obese rats. Experiments measuring electrically evoked dopamine signal ex vivo in nucleus accumbens slices showed a much weaker response in obese animals (12 vs. 25x10(6) dopamine molecules per stimulation, P<0.05). The results demonstrate that deficits in mesolimbic dopamine neurotransmission are linked to dietary obesity. Depressed dopamine release may lead obese animals to compensate by eating palatable "comfort" food, a stimulus that released dopamine when laboratory chow failed.

Author information

Author/s: Geiger, B M (BM); Haburcak, M (M); Avena, N M (NM); Moyer, M C (MC); Hoebel, B G (BG); Pothos, E N (EN);

Affiliation: Department of Pharmacology and Experimental Therapeutics and Program in Neuroscience, Tufts University School of Medicine, Boston, MA 02111, USA.

Grants: DK065872 (Agency:NIDDK NIH HHS) ; F31 DA023760 (Agency:NIDA NIH HHS) ; F31 DA023760-01 (Agency:NIDA NIH HHS) ; F31 DA023760-02 (Agency:NIDA NIH HHS) ; P30 NS047243 (Agency:NINDS NIH HHS) ; R01 DK065872-04 (Agency:NIDDK NIH HHS)

Journal and publication information

Publication Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Neuroscience (Neuroscience), published in United States. (Language: eng)

Reference: 2009-Apr; vol 159 (issue 4) : pp 1193-9

Dates: Created 2009/05/05; Completed 2009/08/20;

PMID: 19409204, status: MEDLINE (last retrieval date: 8/21/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Feeding Behavior - physiology
Female
Limbic System - drug effects; physiopathology
Nucleus Accumbens - drug effects; physiopathology
Obesity - physiopathology
Potassium Chloride - administration & dosage
Rats
Rats, Sprague-Dawley
Synaptic Transmission - drug effects; physiology

Associated Chemicals: Central Nervous System Agents (0) ; Dopamine Uptake Inhibitors (0) ; Dextroamphetamine (51-64-9) ; Potassium Chloride (7447-40-7)

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