Hostname: page-component-cd9895bd7-hc48f Total loading time: 0 Render date: 2024-12-29T07:55:06.544Z Has data issue: false hasContentIssue false
  • English
  • Français

Mesolimbic dopamine and its neuromodulators in obesity and binge eating

Published online by Cambridge University Press:  30 October 2015

Lindsay Naef ,
Kimberley A. Pitman  and
Stephanie L. Borgland
Lindsay Naef
Affiliation:
Department of Physiology & Pharmacology, Cumming School of Medicine, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
Kimberley A. Pitman
Affiliation:
Department of Physiology & Pharmacology, Cumming School of Medicine, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
Stephanie L. Borgland*
Affiliation:
Department of Physiology & Pharmacology, Cumming School of Medicine, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
*
*Address for correspondence: Stephanie Borgland, PhD, 3330 Hospital Drive Northwest, Calgary, Alberta T2N 4N1, Canada. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Obesity has reached epidemic prevalence, and much research has focused on homeostatic and nonhomeostatic mechanisms underlying overconsumption of food. Mesocorticolimbic circuitry, including dopamine neurons of the ventral tegmental area (VTA), is a key substrate for nonhomeostatic feeding. The goal of the present review is to compare changes in mesolimbic dopamine function in human obesity with diet-induced obesity in rodents. Additionally, we will review the literature to determine if dopamine signaling is altered with binge eating disorder in humans or binge eating modeled in rodents. Finally, we assess modulation of dopamine neurons by neuropeptides and peripheral peptidergic signals that occur with obesity or binge eating. We find that while decreased dopamine concentration is observed with obesity, there is inconsistency outside the human literature on the relationship between striatal D2 receptor expression and obesity. Finally, few studies have explored how orexigenic or anorexigenic peptides modulate dopamine neuronal activity or striatal dopamine in obese models. However, ghrelin modulation of dopamine neurons may be an important factor for driving binge feeding in rodents.

Keywords

Diet-induced obesityhormonesmesolimbic dopamineneuropeptidesstriatumventral tegmental area
Type
Review Articles
Information
CNS Spectrums , Volume 20 , Special Issue 6: Binge Eating Disorder Differentiating from General Obesity , December 2015 , pp. 574 - 583
Copyright
© Cambridge University Press 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Beier, KT, Steinberg, EE, DeLoach, KE, et al. Circuit architecture of VTA dopamine neurons revealed by systematic input-output mapping. Cell. 2015; 162(3): 622–634.Google Scholar
2. Di Chiara, G, Imperato, A. Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci U S A. 1988; 85(14): 5274–5278.Google Scholar
3. Call, C, Walsh, BT, Attia, E. From DSM-IV to DSM-5: changes to eating disorder diagnoses. Curr Opin Psychiatry. 2013; 26(6): 532–536.CrossRefGoogle ScholarPubMed
4. Woods, SC, Seeley, RJ, Rushing, PA, D’Alessio, D, Tso, P. A controlled high-fat diet induces an obese syndrome in rats. J Nutr. 2003; 133(4): 1081–1087.Google Scholar
5. Stice, E, Spoor, S, Bohon, C, Small, DM. Relation between obesity and blunted striatal response to food is moderated by TaqIA A1 allele. Science. 2008; 322(5900): 449–452.Google Scholar
6. Stice, E, Spoor, S, Bohon, C, Veldhuizen, MG, Small, DM. Relation of reward from food intake and anticipated food intake to obesity: a functional magnetic resonance imaging study. J Abnorm Psychol. 2008; 117(4): 924–935.CrossRefGoogle ScholarPubMed
7. Green, E, Jacobson, A, Haase, L, Murphy, C. Reduced nucleus accumbens and caudate nucleus activation to a pleasant taste is associated with obesity in older adults. Brain Res. 2011; 1386: 109–117.CrossRefGoogle ScholarPubMed
8. Frank, GKW, Reynolds, JR, Shott, ME, et al. Anorexia nervosa and obesity are associated with opposite brain reward response. Neuropsychopharmacology. 2012; 37(9): 2031–2046.Google Scholar
9. Martin, LE, Holsen, LM, Chambers, RJ, et al. Neural mechanisms associated with food motivation in obese and healthy weight adults. Obesity (Silver Spring). 2010; 18(2): 254–260.Google Scholar
10. Rothemund, Y, Preuschhof, C, Bohner, G, et al. Differential activation of the dorsal striatum by high-calorie visual food stimuli in obese individuals. Neuroimage. 2007; 37(2): 410–421.Google Scholar
11. Stoeckel, LE, Kim, J, Weller, RE, Cox, JE, Cook, EW, Horwitz, B. Effective connectivity of a reward network in obese women. Brain Res Bull. 2009; 79(6): 388–395.Google Scholar
12. Carnell, S, Gibson, C, Benson, L, Ochner, CN, Geliebter, A. Neuroimaging and obesity: current knowledge and future directions. Obes Rev. 2012; 13(1): 43–56.Google Scholar
13. Li, Y, South, T, Han, M, Chen, J, Wang, R, Huang, X-F. High-fat diet decreases tyrosine hydroxylase mRNA expression irrespective of obesity susceptibility in mice. Brain Res. 2009; 1268: 181–189.CrossRefGoogle ScholarPubMed
14. Ong, ZY, Wanasuria, AF, Lin, MZP, Hiscock, J, Muhlhausler, BS. Chronic intake of a cafeteria diet and subsequent abstinence: sex-specific effects on gene expression in the mesolimbic reward system. Appetite. 2013; 65: 189–199.Google Scholar
15. Ahmed, S, Kashem, MA, Sarker, R, Ahmed, EU, Hargreaves, GA, McGregor, IS. Neuroadaptations in the striatal proteome of the rat following prolonged excessive sucrose intake. Neurochem Res. 2014; 39(5): 815–824.Google Scholar
16. Davis, JF, Tracy, AL, Schurdak, JD, et al. Exposure to elevated levels of dietary fat attenuates psychostimulant reward and mesolimbic dopamine turnover in the rat. Behav Neurosci. 2008; 122(6): 1257–1263.Google Scholar
17. Zhang, C, Wei, N-L, Wang, Y, Wang, X, Zhang, J-G, Zhang, K. Deep brain stimulation of the nucleus accumbens shell induces anti-obesity effects in obese rats with alteration of dopamine neurotransmission. Neurosci Lett. 2015; 589: 1–6.CrossRefGoogle ScholarPubMed
18. Hansen, HH, Jensen, MM, Overgaard, A, Weikop, P, Mikkelsen, JD. Tesofensine induces appetite suppression and weight loss with reversal of low forebrain dopamine levels in the diet-induced obese rat. Pharmacol Biochem Behav. 2013; 110: 265–271.Google Scholar
19. Geiger, BM, Haburcak, M, Avena, NM, Moyer, MC, Hoebel, BG, Pothos, EN. Deficits of mesolimbic dopamine neurotransmission in rat dietary obesity. Neuroscience. 2009; 159(4): 1193–1199.Google Scholar
20. Narayanaswami, V, Thompson, AC, Cassis, LA, Bardo, MT, Dwoskin, LP. Diet-induced obesity: dopamine transporter function, impulsivity and motivation. Int J Obes (Lond). 2013; 37(8): 1095–1103.Google Scholar
21. Wang, G-J, Geliebter, A, Volkow, ND, et al. Enhanced striatal dopamine release during food stimulation in binge eating disorder. Obesity (Silver Spring). 2011; 19(8): 1601–1608.CrossRefGoogle ScholarPubMed
22. Rada, P, Avena, NM, Hoebel, BG. Daily bingeing on sugar repeatedly releases dopamine in the accumbens shell. Neuroscience. 2005; 134(3): 737–744.CrossRefGoogle ScholarPubMed
23. Hajnal, A, Norgren, R. Repeated access to sucrose augments dopamine turnover in the nucleus accumbens. Neuroreport. 2002; 13(17): 2213–2216.Google Scholar
24. Carr, KD. Chronic food restriction: enhancing effects on drug reward and striatal cell signaling. Physiol Behav. 2007; 91(5): 459–472.Google Scholar
25. Valdivia, S, Cornejo, MP, Reynaldo, M, De Francesco, PN, Perello, M. Escalation in high fat intake in a binge eating model differentially engages dopamine neurons of the ventral tegmental area and requires ghrelin signaling. Psychoneuroendocrinology. 2015; 60: 206–216.Google Scholar
26. de Weijer, BA, van de Giessen, E, van Amelsvoort, TA, et al. Lower striatal dopamine D2/3 receptor availability in obese compared with non-obese subjects. EJNMMI Res. 2011; 1(1): 37.Google Scholar
27. Haltia, LT, Rinne, JO, Merisaari, H, et al. Effects of intravenous glucose on dopaminergic function in the human brain in vivo. Synapse. 2007; 61(9): 748–756.Google Scholar
28. Wang, GJ, Volkow, ND, Logan, J, et al. Brain dopamine and obesity. Lancet. 2001; 357(9253): 354–357.CrossRefGoogle ScholarPubMed
29. Dunn, JP, Kessler, RM, Feurer, ID, et al. Relationship of dopamine type 2 receptor binding potential with fasting neuroendocrine hormones and insulin sensitivity in human obesity. Diabetes Care. 2012; 35(5): 1105–1111.Google Scholar
30. Kung, HF, Pan, S, Kung, MP, et al. In vitro and in vivo evaluation of [123I]IBZM: a potential CNS D-2 dopamine receptor imaging agent. J Nucl Med. 1989; 30(1): 88–92.Google Scholar
31. Guo, J, Simmons, WK, Herscovitch, P, Martin, A, Hall, KD. Striatal dopamine D2-like receptor correlation patterns with human obesity and opportunistic eating behavior. Mol Psychiatry. 2014; 19(10): 1078–1084.CrossRefGoogle ScholarPubMed
32. Fossella, J, Green, AE, Fan, J. Evaluation of a structural polymorphism in the ankyrin repeat and kinase domain containing 1 (ANKK1) gene and the activation of executive attention networks. Cogn Affect Behav Neurosci. 2006; 6(1): 71–78.Google Scholar
33. Ritchie, T, Noble, EP. Association of seven polymorphisms of the D2 dopamine receptor gene with brain receptor-binding characteristics. Neurochem Res. 2003; 28(1): 73–82.Google Scholar
34. Roth, CL, Hinney, A, Schur, EA, Elfers, CT, Reinehr, T. Association analyses for dopamine receptor gene polymorphisms and weight status in a longitudinal analysis in obese children before and after lifestyle intervention. BMC Pediatr. 2013; 13: 197.CrossRefGoogle Scholar
35. Thomas, GN, Critchley, JA, Tomlinson, B, Cockram, CS, Chan, JC. Relationships between the taqI polymorphism of the dopamine D2 receptor and blood pressure in hyperglycaemic and normoglycaemic Chinese subjects. Clin Endocrinol (Oxf). 2001; 55(5): 605–611.CrossRefGoogle ScholarPubMed
36. Southon, A, Walder, K, Sanigorski, AM, et al. The Taq IA and Ser311 Cys polymorphisms in the dopamine D2 receptor gene and obesity. Diabetes Nutr Metab. 2003; 16(1): 72–76.Google Scholar
37. Kaplan, AS, Levitan, RD, Yilmaz, Z, Davis, C, Tharmalingam, S, Kennedy, JL. A DRD4/BDNF gene-gene interaction associated with maximum BMI in women with bulimia nervosa. Int J Eat Disord. 2008; 41(1): 22–28.Google Scholar
38. Johnson, PM, Kenny, PJ. Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat Neurosci. 2010; 13(5): 635–641.Google Scholar
39. Hajnal, A, Margas, WM, Covasa, M. Altered dopamine D2 receptor function and binding in obese OLETF rat. Brain Res Bull. 2008; 75(1): 70–76.Google Scholar
40. Colantuoni, C, Schwenker, J, McCarthy, J, et al. Excessive sugar intake alters binding to dopamine and mu-opioid receptors in the brain. Neuroreport. 2001; 12(16): 3549–3552.CrossRefGoogle ScholarPubMed
41. Huang, X-F, Yu, Y, Zavitsanou, K, Han, M, Storlien, L. Differential expression of dopamine D2 and D4 receptor and tyrosine hydroxylase mRNA in mice prone, or resistant, to chronic high-fat diet-induced obesity. Brain Res Mol Brain Res. 2005; 135(1–2): 150–161.Google Scholar
42. South, T, Huang, X-F. High-fat diet exposure increases dopamine D2 receptor and decreases dopamine transporter receptor binding density in the nucleus accumbens and caudate putamen of mice. Neurochem Res. 2008; 33(3): 598–605.Google Scholar
43. Sharma, S, Fulton, S. Diet-induced obesity promotes depressive-like behaviour that is associated with neural adaptations in brain reward circuitry. Int J Obes (Lond). 2013; 37(3): 382–389.Google Scholar
44. van de Giessen, E, la Fleur, SE, de Bruin, K, van den Brink, W, Booij, J. Free-choice and no-choice high-fat diets affect striatal dopamine D2/3 receptor availability, caloric intake, and adiposity. Obesity (Silver Spring). 2012; 20(8): 1738–1740.Google Scholar
45. van de Giessen, E, la Fleur, SE, Eggels, L, de Bruin, K, van den Brink, W, Booij, J. High fat/carbohydrate ratio but not total energy intake induces lower striatal dopamine D2/3 receptor availability in diet-induced obesity. Int J Obes (Lond). 2013; 37(5): 754–757.CrossRefGoogle Scholar
46. Davis, CA, Levitan, RD, Reid, C, et al. Dopamine for “wanting” and opioids for “liking”: a comparison of obese adults with and without binge eating. Obesity (Silver Spring). 2009; 17(6): 1220–1225.Google Scholar
47. Bello, NT, Lucas, LR, Hajnal, A. Repeated sucrose access influences dopamine D2 receptor density in the striatum. Neuroreport. 2002; 13(12): 1575–1578.Google Scholar
48. Thomsen, G, Ziebell, M, Jensen, PS, da Cuhna-Bang, S, Knudsen, GM, Pinborg, LH. No correlation between body mass index and striatal dopamine transporter availability in healthy volunteers using SPECT and [123I]PE2I. Obesity (Silver Spring). 2013; 21(9): 1803–1806.Google Scholar
49. van de Giessen, E, Hesse, S, Caan, MWA, et al. No association between striatal dopamine transporter binding and body mass index: a multi-center European study in healthy volunteers. Neuroimage. 2013; 64: 61–67.CrossRefGoogle ScholarPubMed
50. Chen, PS, Yang, YK, Yeh, TL, et al. Correlation between body mass index and striatal dopamine transporter availability in healthy volunteers—a SPECT study. Neuroimage. 2008; 40(1): 275–279.Google Scholar
51. Cone, JJ, Chartoff, EH, Potter, DN, Ebner, SR, Roitman, MF. Prolonged high fat diet reduces dopamine reuptake without altering DAT gene expression. PloS One. 2013; 8(3): e58251.Google Scholar
52. Perry, ML, Leinninger, GM, Chen, R, et al. Leptin promotes dopamine transporter and tyrosine hydroxylase activity in the nucleus accumbens of Sprague-Dawley rats. J Neurochem. 2010; 114(3): 666–674.Google Scholar
53. Mebel, DM, Wong, JCY, Dong, YJ, Borgland, SL. Insulin in the ventral tegmental area reduces hedonic feeding and suppresses dopamine concentration via increased reuptake. Eur J Neurosci. 2012; 36(3): 2336–2346.Google Scholar
54. Hryhorczuk, C, Florea, M, Rodaros, D, et al. Dampened mesolimbic dopamine function and signaling by saturated but not monounsaturated dietary lipids. Neuropsychopharmacology. In press. DOI: 10.1038/npp.2015.207.Google Scholar
55. Shinohara, M, Mizushima, H, Hirano, M, et al. Eating disorders with binge-eating behaviour are associated with the s allele of the 3′-UTR VNTR polymorphism of the dopamine transporter gene. J Psychiatry Neurosci. 2004; 29(2): 134–137.Google Scholar
56. Davis, C, Levitan, RD, Kaplan, AS, et al. Dopamine transporter gene (DAT1) associated with appetite suppression to methylphenidate in a case-control study of binge eating disorder. Neuropsychopharmacology. 2007; 32(10): 2199–2206.CrossRefGoogle Scholar
57. Bello, NT, Sweigart, KL, Lakoski, JM, Norgren, R, Hajnal, A. Restricted feeding with scheduled sucrose access results in an upregulation of the rat dopamine transporter. Am J Physiol Regul Integr Comp Physiol. 2003; 284(5): R1260–R1268.Google Scholar
58. Blum, K, Sheridan, PJ, Wood, RC, et al. The D2 dopamine receptor gene as a determinant of reward deficiency syndrome. J R Soc Med. 1996; 89(7): 396–400.Google Scholar
59. Beeler, JA, Faust, RP, Turkson, S, Ye, H, Zhuang, X. Low dopamine D2 receptor increases vulnerability to obesity via reduced physical activity not increased appetitive motivation. Biol Psychiatry. In press. DOI: 10.1016/j.biopsych.2015.07.009.Google Scholar
60. Liu, S, Borgland, SL. Regulation of the mesolimbic dopamine circuit by feeding peptides. Neuroscience. 2015; 289: 19–42.Google Scholar
61. Kojima, M, Hosoda, H, Date, Y, Nakazato, M, Matsuo, H, Kangawa, K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999; 402(6762): 656–660.Google Scholar
62. Cummings, DE. Ghrelin and the short- and long-term regulation of appetite and body weight. Physiol Behav. 2006; 89(1): 71–84.Google Scholar
63. Jerlhag, E, Egecioglu, E, Dickson, SL, Douhan, A, Svensson, L, Engel, JA. Ghrelin administration into tegmental areas stimulates locomotor activity and increases extracellular concentration of dopamine in the nucleus accumbens. Addict Biol. 2007; 12(1): 6–16.CrossRefGoogle ScholarPubMed
64. Naleid, AM, Grace, MK, Cummings, DE, Levine, AS. Ghrelin induces feeding in the mesolimbic reward pathway between the ventral tegmental area and the nucleus accumbens. Peptides. 2005; 26(11): 2274–2279.Google Scholar
65. Kawahara, Y, Kawahara, H, Kaneko, F, et al. Peripherally administered ghrelin induces bimodal effects on the mesolimbic dopamine system depending on food-consumptive states. Neuroscience. 2009; 161(3): 855–864.Google Scholar
66. Skibicka, KP, Hansson, C, Alvarez-Crespo, M, Friberg, PA, Dickson, SL. Ghrelin directly targets the ventral tegmental area to increase food motivation. Neuroscience. 2011; 180: 129–137.Google Scholar
67. Egecioglu, E, Jerlhag, E, Salomé, N, et al. Ghrelin increases intake of rewarding food in rodents. Addict Biol. 2010; 15(3): 304–311.Google Scholar
68. Abizaid, A, Liu, Z-W, Andrews, ZB, et al. Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite. J Clin Invest. 2006; 116(12): 3229–3239.Google Scholar
69. Quarta, D, Di Francesco, C, Melotto, S, Mangiarini, L, Heidbreder, C, Hedou, G. Systemic administration of ghrelin increases extracellular dopamine in the shell but not the core subdivision of the nucleus accumbens. Neurochem Int. 2009; 54(2): 89–94.Google Scholar
70. Cone, JJ, Roitman, JD, Roitman, MF. Ghrelin regulates phasic dopamine and nucleus accumbens signaling evoked by food-predictive stimuli. J Neurochem. 2015; 133(6): 844–856.Google Scholar
71. Moesgaard, SG, Ahrén, B, Carr, RD, Gram, DX, Brand, CL, Sundler, F. Effects of high-fat feeding and fasting on ghrelin expression in the mouse stomach. Regul Pept. 2004; 120(1–3): 261–267.Google Scholar
72. Perreault, M, Istrate, N, Wang, L, Nichols, AJ, Tozzo, E, Stricker-Krongrad, A. Resistance to the orexigenic effect of ghrelin in dietary-induced obesity in mice: reversal upon weight loss. Int J Obes (Lond). 2004; 28(7): 879–885.Google Scholar
73. Lindqvist, A, de la Cour, CD, Stegmark, A, Håkanson, R, Erlanson-Albertsson, C. Overeating of palatable food is associated with blunted leptin and ghrelin responses. Regul Pept. 2005; 130(3): 123–132.Google Scholar
74. Williams, DL, Grill, HJ, Cummings, DE, Kaplan, JM. Overfeeding-induced weight gain suppresses plasma ghrelin levels in rats. J Endocrinol Invest. 2006; 29(10): 863–868.Google Scholar
75. Murray, S, Tulloch, A, Gold, MS, Avena, NM. Hormonal and neural mechanisms of food reward, eating behaviour and obesity. Nat Rev Endocrinol. 2014; 10(9): 540–552.Google Scholar
76. van Zessen, R, van der Plasse, G, Adan, RA. Contribution of the mesolimbic dopamine system in mediating the effects of leptin and ghrelin on feeding. Proc Nutr Soc. 2012; 71(4): 435–445.Google Scholar
77. Mahler, SV, Moorman, DE, Smith, RJ, James, MH, Aston-Jones, G. Motivational activation: a unifying hypothesis of orexin/hypocretin function. Nat Neurosci. 2014; 17(10): 1298–1303.Google Scholar
78. Perello, M, Sakata, I, Birnbaum, S, et al. Ghrelin increases the rewarding value of high-fat diet in an orexin-dependent manner. Biol Psychiatry. 2010; 67(9): 880–886.Google Scholar
79. Cone, JJ, McCutcheon, JE, Roitman, MF. Ghrelin acts as an interface between physiological state and phasic dopamine signaling. J Neurosci. 2014; 34(14): 4905–4913.Google Scholar
80. Thompson, JL, Borgland, SL. A role for hypocretin/orexin in motivation. Behav Brain Res. 2011; 217(2): 446–453.Google Scholar
81. Korotkova, TM, Sergeeva, OA, Eriksson, KS, Haas, HL, Brown, RE. Excitation of ventral tegmental area dopaminergic and nondopaminergic neurons by orexins/hypocretins. J Neurosci. 2003; 23(1): 7–11.Google Scholar
82. Borgland, SL, Taha, SA, Sarti, F, Fields, HL, Bonci, A. Orexin A in the VTA is critical for the induction of synaptic plasticity and behavioral sensitization to cocaine. Neuron. 2006; 49(4): 589–601.Google Scholar
83. Vittoz, NM, Berridge, CW. Hypocretin/orexin selectively increases dopamine efflux within the prefrontal cortex: involvement of the ventral tegmental area. Neuropsychopharmacology. 2006; 31(2): 384–395.Google Scholar
84. España, RA, Oleson, EB, Locke, JL, Brookshire, BR, Roberts, DCS, Jones, SR. The hypocretin-orexin system regulates cocaine self-administration via actions on the mesolimbic dopamine system. Eur J Neurosci. 2010; 31(2): 336–348.Google Scholar
85. Borgland, SL, Chang, S-J, Bowers, MS, et al. Orexin A/hypocretin-1 selectively promotes motivation for positive reinforcers. J Neurosci. 2009; 29(36): 11215–11225.Google Scholar
86. Teske, JA, Levine, AS, Kuskowski, M, Levine, JA, Kotz, CM. Elevated hypothalamic orexin signaling, sensitivity to orexin A, and spontaneous physical activity in obesity-resistant rats. Am J Physiol Regul Integr Comp Physiol. 2006; 291(4): R889–R899.Google Scholar
87. Funato, H, Tsai, AL, Willie, JT, et al. Enhanced orexin receptor-2 signaling prevents diet-induced obesity and improves leptin sensitivity. Cell Metab. 2009; 9(1): 64–76.Google Scholar
88. Nobunaga, M, Obukuro, K, Kurauchi, Y, et al. High fat diet induces specific pathological changes in hypothalamic orexin neurons in mice. Neurochem Int. 2014; 78: 61–66.Google Scholar
89. Zhu, Y, Yamanaka, A, Kunii, K, Tsujino, N, Goto, K, Sakurai, T. Orexin-mediated feeding behavior involves both leptin-sensitive and -insensitive pathways. Physiol Behav. 2002; 77(2–3): 251–257.Google Scholar
90. Horvath, TL, Gao, X-B. Input organization and plasticity of hypocretin neurons: possible clues to obesity’s association with insomnia. Cell Metab. 2005; 1(4): 279–286.Google Scholar
91. Cristino, L, Busetto, G, Imperatore, R, et al. Obesity-driven synaptic remodeling affects endocannabinoid control of orexinergic neurons. Proc Natl Acad Sci U S A. 2013; 110(24): E2229–E2238.Google Scholar
92. Teegarden, SL, Nestler, EJ, Bale, TL. Delta FosB-mediated alterations in dopamine signaling are normalized by a palatable high-fat diet. Biol Psychiatry. 2008; 64(11): 941–950.Google Scholar
93. Valdivia, S, Patrone, A, Reynaldo, M, Perello, M. Acute high fat diet consumption activates the mesolimbic circuit and requires orexin signaling in a mouse model. PloS One. 2014; 9(1): e87478.Google Scholar
94. Ahima, RS, Flier, JS. Leptin. Annu Rev Physiol. 2000; 62: 413–437.Google Scholar
95. El-Haschimi, K, Pierroz, DD, Hileman, SM, Bjørbaek, C, Flier, JS. Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity. J Clin Invest. 2000; 105(12): 1827–1832.Google Scholar
96. Trinko, R, Gan, G, Gao, X-B, Sears, RM, Guarnieri, DJ, DiLeone, RJ. Erk1/2 mediates leptin receptor signaling in the ventral tegmental area. PloS One. 2011; 6(11): e27180.Google Scholar
97. Hommel, JD, Trinko, R, Sears, RM, et al. Leptin receptor signaling in midbrain dopamine neurons regulates feeding. Neuron. 2006; 51(6): 801–810.Google Scholar
98. Thompson, JL, Borgland, SL. Presynaptic leptin action suppresses excitatory synaptic transmission onto ventral tegmental area dopamine neurons. Biol Psychiatry. 2013; 73(9): 860–868.Google Scholar
99. Krügel, U, Schraft, T, Kittner, H, Kiess, W, Illes, P. Basal and feeding-evoked dopamine release in the rat nucleus accumbens is depressed by leptin. Eur J Pharmacol. 2003; 482(1–3): 185–187.Google Scholar
100. van der Plasse, G, van Zessen, R, Luijendijk, MCM, et al. Modulation of cue-induced firing of ventral tegmental area dopamine neurons by leptin and ghrelin. Int J Obes (Lond). In press. DOI: 10.1038/ijo.2015.131.Google Scholar
101. Fulton, S, Pissios, P, Manchon, RP, et al. Leptin regulation of the mesoaccumbens dopamine pathway. Neuron. 2006; 51(6): 811–822.Google Scholar
102. Roseberry, AG, Painter, T, Mark, GP, Williams, JT. Decreased vesicular somatodendritic dopamine stores in leptin-deficient mice. J Neurosci. 2007; 27(26): 7021–7027.Google Scholar
103. Matheny, M, Shapiro, A, Tümer, N, Scarpace, PJ. Region-specific diet-induced and leptin-induced cellular leptin resistance includes the ventral tegmental area in rats. Neuropharmacology. 2011; 60(2–3): 480–487.Google Scholar
104. Bruijnzeel, AW, Qi, X, Corrie, LW. Anorexic effects of intra-VTA leptin are similar in low-fat and high-fat-fed rats but attenuated in a subgroup of high-fat-fed obese rats. Pharmacol Biochem Behav. 2013; 103(3): 573–581.Google Scholar
105. van den Heuvel, JK, Eggels, L, Fliers, E, Kalsbeek, A, Adan, RAH, la Fleur, SE. Differential modulation of arcuate nucleus and mesolimbic gene expression levels by central leptin in rats on short-term high-fat high-sugar diet. PloS One. 2014; 9(1): e87729 doi:10.1371/journal.pone.0087729.Google Scholar
106. Powley, TL. The ventromedial hypothalamic syndrome, satiety, and a cephalic phase hypothesis. Psychol Rev. 1977; 84(1): 89–126.Google Scholar
107. McGowan, MK, Andrews, KM, Grossman, SP. Chronic intrahypothalamic infusions of insulin or insulin antibodies alter body weight and food intake in the rat. Physiol Behav. 1992; 51(4): 753–766.Google Scholar
108. Figlewicz, DP, Evans, SB, Murphy, J, Hoen, M, Baskin, DG. Expression of receptors for insulin and leptin in the ventral tegmental area/substantia nigra (VTA/SN) of the rat. Brain Res. 2003; 964(1): 107–115.Google Scholar
109. Pardini, AW, Nguyen, HT, Figlewicz, DP, et al. Distribution of insulin receptor substrate-2 in brain areas involved in energy homeostasis. Brain Res. 2006; 1112(1): 169–178.Google Scholar
110. Liu, S, Labouèbe, G, Karunakaran, S, Clee, SM, Borgland, SL. Effect of insulin on excitatory synaptic transmission onto dopamine neurons of the ventral tegmental area in a mouse model of hyperinsulinemia. Nutr Diabetes. 2013; 3: e97.Google Scholar
111. Labouèbe, G, Liu, S, Dias, C, et al. Insulin induces long-term depression of ventral tegmental area dopamine neurons via endocannabinoids. Nat Neurosci. 2013; 16(3): 300–308.Google Scholar
112. Bruijnzeel, AW, Corrie, LW, Rogers, JA, Yamada, H. Effects of insulin and leptin in the ventral tegmental area and arcuate hypothalamic nucleus on food intake and brain reward function in female rats. Behav Brain Res. 2011; 219(2): 254–264.Google Scholar
113. Könner, AC, Hess, S, Tovar, S, et al. Role for insulin signaling in catecholaminergic neurons in control of energy homeostasis. Cell Metab. 2011; 13(6): 720–728.Google Scholar
114. Portella, AK, Silveira, PP, Laureano, DP, et al. Litter size reduction alters insulin signaling in the ventral tegmental area and influences dopamine-related behaviors in adult rats. Behav Brain Res. 2015; 278: 66–73.Google Scholar
115. Steculorum, SM, Solas, M, Brüning, JC. The paradox of neuronal insulin action and resistance in the development of aging-associated diseases. Alzheimers Dement. 2014; 10(1 Suppl): S3–S11.Google Scholar
116. Rinaman, L. Ascending projections from the caudal visceral nucleus of the solitary tract to brain regions involved in food intake and energy expenditure. Brain Res. 2010; 1350: 18–34.Google Scholar
117. Merchenthaler, I, Lane, M, Shughrue, P. Distribution of pre-pro-glucagon and glucagon-like peptide-1 receptor messenger RNAs in the rat central nervous system. J Comp Neurol. 1999; 403(2): 261–280.Google Scholar
118. Larsen, PJ, Tang-Christensen, M, Holst, JJ, Orskov, C. Distribution of glucagon-like peptide-1 and other preproglucagon-derived peptides in the rat hypothalamus and brainstem. Neuroscience. 1997; 77(1): 257–270.Google Scholar
119. Alhadeff, AL, Rupprecht, LE, Hayes, MR. GLP-1 neurons in the nucleus of the solitary tract project directly to the ventral tegmental area and nucleus accumbens to control for food intake. Endocrinology. 2012; 153(2): 647–658.Google Scholar
120. Campos, RV, Lee, YC, Drucker, DJ. Divergent tissue-specific and developmental expression of receptors for glucagon and glucagon-like peptide-1 in the mouse. Endocrinology. 1994; 134(5): 2156–2164.Google Scholar
121. Mietlicki-Baase, EG, Ortinski, PI, Rupprecht, LE, et al. The food intake-suppressive effects of glucagon-like peptide-1 receptor signaling in the ventral tegmental area are mediated by AMPA/kainate receptors. Am J Physiol Endocrinol Metab. 2013; 305(11): E1367–E1374.Google Scholar
122. Wang, X-F, Liu, J-J, Xia, J, Liu, J, Mirabella, V, Pang, ZP. Endogenous glucagon-like peptide-1 suppresses high-fat food intake by reducing synaptic drive onto mesolimbic dopamine neurons. Cell Rep. 2015; 12(5): 726–733.Google Scholar
123. Heppner, KM, Perez-Tilve, D. GLP-1 based therapeutics: simultaneously combating T2DM and obesity. Front Neurosci. 2015; 9: 92.Google Scholar
124. Chen, H, Simar, D, Morris, MJ. Maternal obesity impairs brain glucose metabolism and neural response to hyperglycemia in male rat offspring. J Neurochem. 2014; 129(2): 297–303.Google Scholar
125. Chan, YL, Saad, S, Simar, D, et al. Short term exendin-4 treatment reduces markers of metabolic disorders in female offspring of obese rat dams. Int J Dev Neurosci. 2015; 46: 67–75.Google Scholar
126. Cao, X, Xu, P, Oyola, MG, et al. Estrogens stimulate serotonin neurons to inhibit binge-like eating in mice. J Clin Invest. 2014; 124(10): 4351–4362.CrossRefGoogle ScholarPubMed
127. Robert, SA, Rohana, AG, Shah, SA, Chinna, K, Wan Mohamud, WN, Kamaruddin, NA. Improvement in binge eating in non-diabetic obese individuals after 3 months of treatment with liraglutide—a pilot study. Obes Res Clin Pract. 2015; 9(3): 301–304.Google Scholar