Skip to main content

Advertisement

SpringerLink
Log in

Neuroadaptations in the Striatal Proteome of the Rat Following Prolonged Excessive Sucrose Intake

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Obesity is a contemporary health problem of rapidly increasing prevalence. One possible cause of obesity is loss of control over consumption of highly palatable foodstuffs, perhaps mirroring the processes involved in drug addiction. Accordingly, the striatum may be a key neural substrate involved in both food and drug craving. We hypothesised here that prolonged exposure to 10 % sucrose solution might cause neuroadaptations in the striatum that are analogous to those previously reported following prolonged exposure to alcohol or recreational drugs. Male Wistar rats were given constant access to 10 % sucrose solution (in addition to normal lab chow and tap water) for 8 months and were compared with control rats receiving no sucrose access. Rats in the sucrose group typically drank more than 100 ml of sucrose solution per day and showed 13 % greater body weight than controls at the end of the 8 months. Striatal dopamine (DA) concentrations were decreased in the sucrose group rats relative to controls. Differential expression of 18 proteins was identified in the striatum of the sucrose group rats relative to controls. Down regulated proteins included pyridoxal phosphate phosphatase, involved in DA synthesis, and glutathione transferase, involved in free radical scavenging. Up regulated proteins included prolactin (which is under negative regulation by DA) and adipose differentiation-related protein, involved in fat synthesis. We hypothesise that DA-related neuroadaptations in the striatum caused by prolonged sucrose intake may partly drive compulsive intake and seeking of high palatability foodstuffs, in a similar way to that observed with drug and alcohol addictions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Swinburn BA, Sacks G, Hall KD, McPherson K, Finegood DT, Moodie ML, Gortmaker SL (2011) The global obesity pandemic: shaped by global drivers and local environments. Lancet 378(9793):804–814

    Article  PubMed  Google Scholar 

  2. Avena NM, Long KA, Hoebel BG (2005) Sugar-dependent rats show enhanced responding for sugar after abstinence: evidence of a sugar deprivation effect. Physiol Behav 84(3):359–362

    Article  PubMed  CAS  Google Scholar 

  3. Avena NM, Rada P, Hoebel BG (2008) Evidence for sugar addiction: behavioral and neurochemical effects of intermittent, excessive sugar intake. Neurosci Biobehav Rev 32(1):20–39

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  4. Bocarsly ME, Berner LA, Hoebel BG, Avena NM (2011) Rats that binge eat fat-rich food do not show somatic signs or anxiety associated with opiate-like withdrawal: implications for nutrient-specific food addiction behaviors. Physiol Behav 104(5):865–872

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  5. Corwin RL, Avena NM, Boggiano MM (2011) Feeding and reward: perspectives from three rat models of binge eating. Physiol Behav 104(1):87–97

    Article  PubMed  CAS  Google Scholar 

  6. Geiger BM, Haburcak M, Avena NM, Moyer MC, Hoebel BG, Pothos EN (2009) Deficits of mesolimbic dopamine neurotransmission in rat dietary obesity. Neuroscience 159(4):1193–1199

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  7. Baldo BA, Pratt WE, Will MJ, Hanlon EC, Bakshi VP, Cador M (2013) Principles of motivation revealed by the diverse functions of neuropharmacological and neuroanatomical substrates underlying feeding behavior. Neurosci Biobehav Rev 37(9):1985–1998

    Google Scholar 

  8. Carnell S, Gibson C, Benson L, Ochner CN, Geliebter A (2012) Neuroimaging and obesity: current knowledge and future directions. Obes Rev 13(1):43–56

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  9. O’Doherty JP, Deichmann R, Critchley HD, Dolan RJ (2002) Neural responses during anticipation of a primary taste reward. Neuron 33(5):815–826

    Article  PubMed  Google Scholar 

  10. Hajnal A, Smith GP, Norgren R (2004) Oral sucrose stimulation increases accumbens dopamine in the rat. Am J Physiol Regul Integr Comp Physiol 286(1):R31–37

    Article  PubMed  CAS  Google Scholar 

  11. Bassareo V, Di Chiara G (1997) Differential influence of associative and nonassociative learning mechanisms on the responsiveness of prefrontal and accumbal dopamine transmission to food stimuli in rats fed ad libitum. J Neurosci 17(2):851–861

    PubMed  CAS  Google Scholar 

  12. Liang NC, Hajnal A, Norgren R (2006) Sham feeding corn oil increases accumbens dopamine in the rat. Am J Physiol Regul Integr Comp Physiol 291(5):R1236–1239

    Article  PubMed  CAS  Google Scholar 

  13. Schur EA, Kleinhans NM, Goldberg J, Buchwald D, Schwartz MW, Maravilla K (2009) Activation in brain energy regulation and reward centers by food cues varies with choice of visual stimulus. Int J Obes (Lond) 33(6):653–661

    Article  CAS  Google Scholar 

  14. Yoganathan P, Karunakaran S, Ho MM, Clee SM (2012) Nutritional regulation of genome-wide association obesity genes in a tissue-dependent manner. Nutr Metab (Lond) 9(1):65

    Article  CAS  Google Scholar 

  15. Vucetic Z, Kimmel J, Totoki K, Hollenbeck E, Reyes TM (2010) Maternal high-fat diet alters methylation and gene expression of dopamine and opioid-related genes. Endocrinology 151(10):4756–4764

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  16. Lee SK, Park SO, Joe CO, Kim YS (2007) Interaction of HCV core protein with 14-3-3epsilon protein releases Bax to activate apoptosis. Biochem Biophys Res Commun 352(3):756–762

    Article  PubMed  CAS  Google Scholar 

  17. Matsuda-Matsumoto H, Iwazaki T, Kashem MA, Harper C, Matsumoto I (2007) Differential protein expression profiles in the hippocampus of human alcoholics. Neurochem Int 51(6–7):370–376

    Article  PubMed  CAS  Google Scholar 

  18. Kashem MA, Sarker R, Des Etages H, Machaalani R, King N, McGregor IS, Matsumoto I (2009) Comparative proteomics in the corpus callosal sub-regions of postmortem human brain. Neurochem Int 55(7):483–490

    Article  PubMed  CAS  Google Scholar 

  19. Kashem MA, James G, Harper C, Wilce P, Matsumoto I (2007) Differential protein expression in the corpus callosum (splenium) of human alcoholics: a proteomics study. Neurochem Int 50(2):450–459

    Article  PubMed  CAS  Google Scholar 

  20. Kashem MA, Harper C, Matsumoto I (2008) Differential protein expression in the corpus callosum (genu) of human alcoholics. Neurochem Int 53(1–2):1–11

    Article  PubMed  CAS  Google Scholar 

  21. Quinn HR, Matsumoto I, Callaghan PD, Long LE, Arnold JC, Gunasekaran N, Thompson MR, Dawson B, Mallet PE, Kashem MA, Matsuda-Matsumoto H, Iwazaki T, McGregor IS (2008) Adolescent rats find repeated Delta(9)-THC less aversive than adult rats but display greater residual cognitive deficits and changes in hippocampal protein expression following exposure. Neuropsychopharmacology 33(5):1113–1126

    Article  PubMed  Google Scholar 

  22. Hargreaves GA, Quinn H, Kashem MA, Matsumoto I, McGregor IS (2009) Proteomic analysis demonstrates adolescent vulnerability to lasting hippocampal changes following chronic alcohol consumption. Alcohol Clin Exp Res 33(1):86–94

    Article  PubMed  CAS  Google Scholar 

  23. van Nieuwenhuijzen PS, Kashem MA, Matsumoto I, Hunt GE, McGregor IS (2010) A long hangover from party drugs: residual proteomic changes in the hippocampus of rats 8 weeks after gamma-hydroxybutyrate (GHB), 3,4-methylenedioxymethamphetamine (MDMA) or their combination. Neurochem Int 56(8):871–877

    Article  PubMed  Google Scholar 

  24. Motbey CP, Karanges E, Li KM, Wilkinson S, Winstock AR, Ramsay J, Hicks C, Kendig MD, Wyatt N, Callaghan PD, McGregor IS (2012) Mephedrone in adolescent rats: residual memory impairment and acute but not lasting 5-HT depletion. PLoS ONE 7(9):e45473

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  25. Kashem MA, Ummehany R, Ukai W, Hashimoto E, Saito T, McGregor IS, Matsumoto I (2009) Effects of typical (haloperidol) and atypical (risperidone) antipsychotic agents on protein expression in rat neural stem cells. Neurochem Int 55(7):558–565

    Article  PubMed  CAS  Google Scholar 

  26. Ahmed EU, Ahmed S, Ukai W, Matsumoto I, Kemp A, McGregor IS, Kashem MA (2012) Antipsychotic induced alteration of growth and proteome of rat neural stem cells. Neurochem Res 37(8):1649–1659

    Article  PubMed  CAS  Google Scholar 

  27. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  PubMed  CAS  Google Scholar 

  28. Kashem MA, Etages HD, Kopitar-Jerala N, McGregor IS, Matsumoto I (2009) Differential protein expression in the corpus callosum (body) of human alcoholic brain. J Neurochem 110(2):486–495

    Article  PubMed  Google Scholar 

  29. Zabel C, Andreew A, Mao L, Hartl D (2008) Protein expression overlap: more important than which proteins change in expression? Expert Rev Proteom 5(2):187–205

    Article  CAS  Google Scholar 

  30. Stanta G, Mucelli SP, Petrera F, Bonin S, Bussolati G (2006) A novel fixative improves opportunities of nucleic acids and proteomic analysis in human archive’s tissues. Diagn Mol Pathol 15(2):115–123

    Article  PubMed  CAS  Google Scholar 

  31. Grimm JW, Barnes J, North K, Collins S, Weber R (2011) A general method for evaluating incubation of sucrose craving in rats. J Vis Exp 57:e3335

    PubMed  Google Scholar 

  32. Kendig MD, Boakes RA, Rooney KB, Corbit LH (2013) Chronic restricted access to 10 % sucrose solution in adolescent and young adult rats impairs spatial memory and alters sensitivity to outcome devaluation. Physiol Behav 120C:164–172

    Article  Google Scholar 

  33. Lombardo YB, D’Alessandro ME, Chicco AG (2006) A long-term sucrose-rich diet increases diacylglycerol content and membrane nPKC theta expression and alters glucose metabolism in skeletal muscle of rats. Nutr Res 26(6):289–296

    Article  Google Scholar 

  34. Charlet K, Beck A, Heinz A (2013) The dopamine system in mediating alcohol effects in humans. Curr Top Behav Neurosci 13:461–488

    Article  PubMed  CAS  Google Scholar 

  35. Rada P, Avena NM, Hoebel BG (2005) Daily bingeing on sugar repeatedly releases dopamine in the accumbens shell. Neuroscience 134(3):737–744

    Article  PubMed  CAS  Google Scholar 

  36. Doyon WM, Ramachandra V, Samson HH, Czachowski CL, Gonzales RA (2004) Accumbal dopamine concentration during operant self-administration of a sucrose or a novel sucrose with ethanol solution. Alcohol 34(2–3):261–271

    Article  PubMed  CAS  Google Scholar 

  37. Hajnal A, Margas WM, Covasa M (2008) Altered dopamine D2 receptor function and binding in obese OLETF rat. Brain Res Bull 75(1):70–76

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  38. Rauhut AS, Fenton L, Bardo MT (2010) Renewal of sucrose-seeking behavior in rats: role of D(2) dopamine receptors. Pharmacol Biochem Behav 96(3):354–362

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  39. Pan Y, Berman Y, Haberny S, Meller E, Carr KD (2006) Synthesis, protein levels, activity, and phosphorylation state of tyrosine hydroxylase in mesoaccumbens and nigrostriatal dopamine pathways of chronically food-restricted rats. Brain Res 1122(1):135–142

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  40. Wallace LJ (2007) A small dopamine permeability of storage vesicle membranes and end product inhibition of tyrosine hydroxylase are sufficient to explain changes occurring in dopamine synthesis and storage after inhibition of neuron firing. Synapse 61(9):715–723

    Article  PubMed  CAS  Google Scholar 

  41. Kashem MA, Ahmed S, Sarker R, Ahmed EU, Hargreaves GA, McGregor IS (2012) Long-term daily access to alcohol alters dopamine-related synthesis and signalling proteins in the rat striatum. Neurochem Int 61(8):1280–1288

    Article  PubMed  CAS  Google Scholar 

  42. Ben-Jonathan N, LaPensee CR, LaPensee EW (2008) What can we learn from rodents about prolactin in humans? Endocr Rev 29(1):1–41

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  43. Shelly S, Boaz M, Orbach H (2012) Prolactin and autoimmunity. Autoimmun Rev 11(6–7):A465–470

    Article  PubMed  CAS  Google Scholar 

  44. Angelier F, Chastel O (2009) Stress, prolactin and parental investment in birds: a review. Gen Comp Endocrinol 163(1–2):142–148

    Article  PubMed  CAS  Google Scholar 

  45. Meaney AM, O’Keane V (2002) Prolactin and schizophrenia: clinical consequences of hyperprolactinemia. Life Sci 71(9):979–992

    Article  PubMed  CAS  Google Scholar 

  46. Tse MC, Wong GK, Xiao P, Cheng CH, Chan KM (2008) Down-regulation of goldfish (Carassius auratus) prolactin gene expression by dopamine and thyrotropin releasing hormone. Gen Comp Endocrinol 155(3):729–741

    Article  PubMed  CAS  Google Scholar 

  47. Gonzalez-Iglesias AE, Murano T, Li S, Tomic M, Stojilkovic SS (2008) Dopamine inhibits basal prolactin release in pituitary lactotrophs through pertussis toxin-sensitive and -insensitive signalling pathways. Endocrinology 149(4):1470–1479

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  48. Ben-Jonathan N, Hugo ER, Brandebourg TD, LaPensee CR (2006) Focus on prolactin as a metabolic hormone. Trends Endocrinol Metab 17(3):110–116

    Article  PubMed  CAS  Google Scholar 

  49. Ellingboe J, Mendelson JH, Kuehnle JC (1980) Effects of heroin and naltrexone on plasma prolactin levels in man. Pharmacol Biochem Behav 12(1):163–165

    Article  PubMed  CAS  Google Scholar 

  50. Brown TT, Dobs AS (2002) Endocrine effects of marijuana. J Clin Pharmacol 42(11 Suppl):90S–96S

    Article  PubMed  CAS  Google Scholar 

  51. Wu LY, Huang EY, Tao PL (2010) Coadministration of dextromethorphan during pregnancy and throughout lactation prevents morphine-induced hyperprolactinemia in female rats. Fertil Steril 93(5):1686–1694

    Article  PubMed  CAS  Google Scholar 

  52. Rideout HJ, Parker LA (1996) Morphine enhancement of sucrose palatability: analysis by the taste reactivity test. Pharmacol Biochem Behav 53(3):731–734

    Article  PubMed  CAS  Google Scholar 

  53. Da Silva LA, De Marcucci OL, Carmona A (1992) Adaptive changes in total pyruvate dehydrogenase activity in lipogenic tissues of rats fed high-sucrose or high-fat diets. Comp Biochem Physiol Comp Physiol 103(2):407–411

    Article  PubMed  Google Scholar 

  54. Pape ME, Lopez-Casillas F, Kim KH (1988) Physiological regulation of acetyl-CoA carboxylase gene expression: effects of diet, diabetes, and lactation on acetyl-CoA carboxylase mRNA. Arch Biochem Biophys 267(1):104–109

    Article  PubMed  CAS  Google Scholar 

  55. Fantino M (2011) Role of lipids in the control of food intake. Curr Opin Clin Nutr Metabol Care 14(2):138–144

    Article  CAS  Google Scholar 

  56. Fortino MA, Lombardo YB, Chicco A (2007) The reduction of dietary sucrose improves dyslipidemia, adiposity, and insulin secretion in an insulin-resistant rat model. Nutrition 23(6):489–497

    Article  PubMed  CAS  Google Scholar 

  57. Basciano H, Federico L, Adeli K (2005) Fructose, insulin resistance, and metabolic dyslipidemia. Nutr Metab (Lond) 2(1):5

    Article  Google Scholar 

  58. Boone C, Mourot J, Gregoire F, Remacle C (2000) The adipose conversion process: regulation by extracellular and intracellular factors. Reprod Nutr Dev 40(4):325–358

    Article  PubMed  CAS  Google Scholar 

  59. Kutsuna M, Kodama T, Sumida M, Nagai A, Higashine M, Zhang W, Hayashi Y, Shiraishi A, Ohashi Y (2007) Presence of adipose differentiation-related protein in rat meibomian gland cells. Exp Eye Res 84(4):687–693

    Article  PubMed  CAS  Google Scholar 

  60. Chirico V, Cannavo S, Lacquaniti A, Salpietro V, Mandolfino M, Romeo PD, Cotta O, Munafo C, Giorgianni G, Salpietro C, Arrigo T (2013) Prolactin in obese children: a bridge between inflammation and metabolic-endocrine dysfunction. Clin Endocrinol (Oxf) 79(4):537–544

    Google Scholar 

  61. Maria Ines PM, Maria LG, Cecilia RM, Daniela N, Maria OA, Marcelo R, Damasia BV (2014) Selective disruption of dopamine D2 receptors in pituitary lactotropes increases body weight and adiposity in female mice. Endocrinology 155(3):829–839

    Google Scholar 

  62. Zhao X, Zhu Q, Wang Y, Yang Z, Liu Y (2010) Tissue-specific expression of the chicken adipose differentiation-related protein (ADP) gene. Mol Biol Rep 37(6):2839–2845

    Article  PubMed  CAS  Google Scholar 

  63. Feillet-Coudray C, Sutra T, Fouret G, Ramos J, Wrutniak-Cabello C, Cabello G, Cristol JP, Coudray C (2009) Oxidative stress in rats fed a high-fat high-sucrose diet and preventive effect of polyphenols: involvement of mitochondrial and NAD(P)H oxidase systems. Free Radic Biol Med 46(5):624–632

    Article  PubMed  CAS  Google Scholar 

  64. Saiki R, Okazaki M, Iwai S, Kumai T, Kobayashi S, Oguchi K (2007) Effects of pioglitazone on increases in visceral fat accumulation and oxidative stress in spontaneously hypertensive hyperlipidemic rats fed a high-fat diet and sucrose solution. J Pharmacol Sci 105(2):157–167

    Article  PubMed  CAS  Google Scholar 

  65. Hansen M, Baunsgaard D, Autrup H, Vogel UB, Moller P, Lindecrona R, Wallin H, Poulsen HE, Loft S, Dragsted LO (2008) Sucrose, glucose and fructose have similar genotoxicity in the rat colon and affect the metabolome. Food Chem Toxicol 46(2):752–760

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The Australian Research Council and National Health and Medical Research Council supported this work via grants to ISM. We acknowledge Sydney University Proteome Research Unit (SUPRU) for providing MALDI-MS facilities. We are grateful to Dr Kong Li for his assistance in the HPLC component of the study.

Conflict of interest

The authors have no conflicts of interest to declare.

Author information

Authors and Affiliations

  1. Psychopharmacology and Proteomics Laboratory, School of Psychology, The University of Sydney, Brennan MacCallum Building (A18), Sydney, NSW, 2006, Australia

    Selina Ahmed, Mohammed Abul Kashem, Ranjana Sarker, Eakhlas U. Ahmed, Garth A. Hargreaves & Iain S. McGregor

Authors
  1. Selina Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohammed Abul Kashem
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ranjana Sarker
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eakhlas U. Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Garth A. Hargreaves
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Iain S. McGregor
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Selina Ahmed.

Additional information

Selina Ahmed and Mohammed Abul Kashem have contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ahmed, S., Kashem, M.A., Sarker, R. et al. Neuroadaptations in the Striatal Proteome of the Rat Following Prolonged Excessive Sucrose Intake. Neurochem Res 39, 815–824 (2014). https://doi.org/10.1007/s11064-014-1274-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-014-1274-6

Keywords

Search

Navigation