Dataset Information

Junk food diet-induced obesity increases D2 receptor autoinhibition in the ventral tegmental area and reduces ethanol drinking.

ABSTRACT: Similar to drugs of abuse, the hedonic value of food is mediated, at least in part, by the mesostriatal dopamine (DA) system. Prolonged intake of either high calorie diets or drugs of abuse both lead to a blunting of the DA system. Most studies have focused on DAergic alterations in the striatum, but little is known about the effects of high calorie diets on ventral tegmental area (VTA) DA neurons. Since high calorie diets produce addictive-like DAergic adaptations, it is possible these diets may increase addiction susceptibility. However, high calorie diets consistently reduce psychostimulant intake and conditioned place preference in rodents. In contrast, high calorie diets can increase or decrease ethanol drinking, but it is not known how a junk food diet (cafeteria diet) affects ethanol drinking. In the current study, we administered a cafeteria diet consisting of bacon, potato chips, cheesecake, cookies, breakfast cereals, marshmallows, and chocolate candies to male Wistar rats for 3-4 weeks, producing an obese phenotype. Prior cafeteria diet feeding reduced homecage ethanol drinking over 2 weeks of testing, and transiently reduced sucrose and chow intake. Importantly, cafeteria diet had no effect on ethanol metabolism rate or blood ethanol concentrations following 2g/kg ethanol administration. In midbrain slices, we showed that cafeteria diet feeding enhances DA D2 receptor (D2R) autoinhibition in VTA DA neurons. These results show that junk food diet-induced obesity reduces ethanol drinking, and suggest that increased D2R autoinhibition in the VTA may contribute to deficits in DAergic signaling and reward hypofunction observed with obesity.

SUBMITTER: Cook JB

PROVIDER: S-EPMC5578487 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Junk food diet-induced obesity increases D2 receptor autoinhibition in the ventral tegmental area and reduces ethanol drinking.

Cook Jason B JB Hendrickson Linzy M LM Garwood Grant M GM Toungate Kelsey M KM Nania Christina V CV Morikawa Hitoshi H

PloS one 20170831 8

Similar to drugs of abuse, the hedonic value of food is mediated, at least in part, by the mesostriatal dopamine (DA) system. Prolonged intake of either high calorie diets or drugs of abuse both lead to a blunting of the DA system. Most studies have focused on DAergic alterations in the striatum, but little is known about the effects of high calorie diets on ventral tegmental area (VTA) DA neurons. Since high calorie diets produce addictive-like DAergic adaptations, it is possible these diets ma ...[more]

PMID: 28859110

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Project description:Alcoholism is characterized by compulsive alcohol intake after a history of chronic consumption. A reduction in mesolimbic dopaminergic transmission observed during abstinence may contribute to the negative affective state that drives compulsive intake. Although previous in vivo recording studies in rodents have demonstrated profound decreases in the firing activity of ventral tegmental area (VTA) dopamine neurons after withdrawal from long-term ethanol exposure, the cellular mechanisms underlying this reduced activity are not well understood. Somatodendritic dopamine release within the VTA exerts powerful feedback inhibition of dopamine neuron activity via stimulation of D(2) autoreceptors and subsequent activation of G protein-gated inwardly rectifying K(+) (GIRK) channels. Here, by performing patch-clamp recordings from putative dopamine neurons in the VTA of mouse brain slices, we show that D(2) receptor/GIRK-mediated inhibition becomes more potent and exhibits less desensitization after withdrawal from repeated in vivo ethanol exposure (2?g/kg, i.p., three times daily for 7 days). In contrast, GABA(B) receptor/GIRK-mediated inhibition and its desensitization are not affected. Chelating cytosolic Ca(2+) with BAPTA augments D(2) inhibition and suppresses its desensitization in control mice, while these effects of BAPTA are occluded in ethanol-treated mice. Furthermore, inositol 1,4,5-trisphosphate (IP(3))-induced intracellular Ca(2+) release and Ca(2+)/calmodulin-dependent protein kinase II are selectively involved in the desensitization of D(2), but not GABA(B), receptor signaling. Consistent with this, activation of metabotropic glutamate receptors that are coupled to IP(3) generation leads to cross-desensitization of D(2)/GIRK-mediated responses. We propose that enhancement of D(2) receptor-mediated autoinhibition via attenuation of a Ca(2+)-dependent desensitization mechanism may contribute to the hypodopaminergic state during ethanol withdrawal.

Dataset Information

Junk food diet-induced obesity increases D2 receptor autoinhibition in the ventral tegmental area and reduces ethanol drinking.

Publications

Junk food diet-induced obesity increases D2 receptor autoinhibition in the ventral tegmental area and reduces ethanol drinking.

Similar Datasets

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