Deficits of mesolimbic dopamine neurotransmission in rat dietary obesity.
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.
Geiger
B M
BM
Department of Pharmacology and Experimental Therapeutics and Program in Neuroscience, Tufts University School of Medicine, Boston, MA 02111, USA.
Haburcak
M
M
Avena
N M
NM
Moyer
M C
MC
Hoebel
B G
BG
Pothos
E N
EN
D000818:Animals; D002491:Central Nervous System Agents / Q000008:administration & dosage; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology; D003913:Dextroamphetamine / Q000008:administration & dosage; D004032:Diet; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D005110:Extracellular Space / Q000378:metabolism; D005247:Feeding Behavior / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D008032:Limbic System / Q000187:drug effects / Q000503:physiopathology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000503:physiopathology; D009765:Obesity / Q000503:physiopathology*; D011189:Potassium Chloride / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D002491:Central Nervous System Agents; D018765:Dopamine Uptake Inhibitors; D011189:Potassium Chloride; D003913:Dextroamphetamine; D004298:Dopamine