PMID- 20875839 OWN - NLM STAT- MEDLINE DCOM- 20111031 LR - 20101118 IS - 1873-7544 (Electronic) IS - 0306-4522 (Linking) VI - 171 IP - 3 DP - 2010 Dec 15 TI - Dopamine D1 receptor gene expression decreases in the nucleus accumbens upon long-term exposure to palatable food and differs depending on diet-induced obesity phenotype in rats. PG - 779-87 LID - 10.1016/j.neuroscience.2010.09.046 [doi] AB - The nucleus accumbens (NAcc) mediates feeding reward; its activity reflects tastants' hedonic value. NAcc dopamine guides immediate responses to reward, however, its involvement in establishing long-term responses after a period of exposure to palatable foods has not been defined. Furthermore, reward-driven overeating propels weight increase, but the scale of weight gain depends on animals' obesity-prone (OP) or -resistant (OR) phenotype. It is unclear whether the NAcc dopamine response to palatable food depends on obesity susceptibility. We investigated the effect of unrestricted extended access to high-fat high-sugar (HFHS) diet on expression of genes encoding dopamine receptors in the NAcc of OP and OR rats. We examined persistence of HFHS diet-induced changes in D(1) and D(2) gene expression in OP and OR rats subjected to HFHS withdrawal (bland chow for 18 days). Effects of restricted access to HFHS by pair-feeding were also studied. Using reverse transcriptase PCR (RT-PCR), we found that NAcc D(1) mRNA was downregulated after long-term HFHS access in OP vs. OR animals. The effect was also observed after 18 days of HFHS withdrawal. Furthermore, restricted HFHS led to downregulation of D(1) as well as of D(2) mRNA levels compared to chow-fed controls. A difference in the expression of mu opioid receptor in the NAcc was also detected between the OP and OR rats during access to palatable food but not after withdrawal. We conclude that exposure to HFHS diets has lasting consequences for the NAcc dopamine system, perhaps modifying the motivation to search for food reward. The fact that the NAcc D(1) expression changes in OP animals after long-term exposure to palatable food and that this effect extends well into the reward discontinuation phase, implicates the D(1) receptor in the propensity to overeat and, in effect, gain weight in obesity prone individuals. CI - Copyright (c) 2010 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Alsio, J AU - Alsio J AD - Department of Neuroscience, Functional Pharmacology, Uppsala University, Biomedical Center, Box 593, SE-751 24, Uppsala, Sweden. johan.alsio@neuro.uu.se FAU - Olszewski, P K AU - Olszewski PK FAU - Norback, A H AU - Norback AH FAU - Gunnarsson, Z E A AU - Gunnarsson ZE FAU - Levine, A S AU - Levine AS FAU - Pickering, C AU - Pickering C FAU - Schioth, H B AU - Schioth HB LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100926 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Receptors, Dopamine D1) SB - IM MH - Animals MH - Appetite Regulation/*genetics MH - Disease Models, Animal MH - Down-Regulation/*genetics/physiology MH - Eating/*genetics MH - Male MH - Nucleus Accumbens/*metabolism/physiopathology MH - Obesity/*genetics/metabolism/physiopathology MH - *Phenotype MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Dopamine D1/*antagonists & inhibitors/*genetics/physiology MH - Time Factors MH - Weight Gain/genetics EDAT- 2010/09/30 06:00 MHDA- 2011/11/01 06:00 CRDT- 2010/09/30 06:00 PHST- 2010/03/05 00:00 [received] PHST- 2010/09/14 00:00 [revised] PHST- 2010/09/27 00:00 [accepted] PHST- 2010/09/30 06:00 [entrez] PHST- 2010/09/30 06:00 [pubmed] PHST- 2011/11/01 06:00 [medline] AID - S0306-4522(10)01294-7 [pii] AID - 10.1016/j.neuroscience.2010.09.046 [doi] PST - ppublish SO - Neuroscience. 2010 Dec 15;171(3):779-87. doi: 10.1016/j.neuroscience.2010.09.046. Epub 2010 Sep 26.