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The impact of periconceptional alcohol exposure on fat preference and gene expression in the mesolimbic reward pathway in adult rat offspring

  • E. S. Dorey (a1), C. L. Cullen (a1) (a2), D. Lucia (a1), K. M. Mah (a1), M.-L. Roy Manchadi (a1), B. S. Muhlhausler (a3) and K. M. Moritz (a1) (a4)...


Alcohol consumption around the time of conception is highly prevalent in Western countries. Exposure to ethanol levels during gestation has been associated with altered development of the mesolimbic reward pathway in rats and increased propensity to addiction, however the effect of exposure only around the time of conception is unknown. The current study investigated the effects of periconceptional alcohol exposure (PC:EtOH) on alcohol and palatable food preferences and gene expression in the ventral tegmental area (VTA) and the nucleus accumbens of the adult offspring. Rats were exposed to a liquid diet containing ethanol (EtOH) (12.5% vol/vol) or a control diet from 4 days before mating until 4 days after mating. PC:EtOH had no effect on alcohol preference in either sex. At 15 months of age, however, male PC:EtOH offspring consumed more high-fat food when compared with male control offspring, but this preference was not observed in females. Expression of the dopamine receptor type 1 (Drd1a) was lower in the VTA of male PC:EtOH offspring compared with their control counterparts. There was no effect of PC:EtOH on mRNA expression of the µ-opioid receptor, tyrosine hydroxylase (Th), dopamine receptor type 2 (Drd2) or dopamine active transporter (Slc6a3). These data support the hypothesis that periconceptional alcohol exposure can alter expression of key components of the mesolimbic reward pathway and heighten the preference of offspring for palatable foods and may therefore increase their propensity towards diet-induced obesity. These results highlight the importance of alcohol avoidance when planning a pregnancy.


Corresponding author

*Address for correspondence: Professor K. Moritz, School of Biomedical Science, The University of Queensland, Brisbane, QLD 4072, Australia. (Email


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1. McCormack, C, Hutchinson, D, Burns, L, et al. Prenatal alcohol consumption between conception and recognition of pregnancy. Alcohol Clin Exp Res. 2017; 41, 369378.
2. Pryor, J, Patrick, SW, Sundermann, AC, Wu, P, Hartmann, KE. Pregnancy intention and maternal alcohol consumption. Obstet Gynecol. 2017; 129, 727733.
3. Riley, EP, Infante, MA, Warren, KR. Fetal alcohol spectrum disorders: an overview. Neuropsychol Rev. 2011; 21, 7380.
4. Alati, R, Al Mamun, A, Williams, GM, et al. In utero alcohol exposure and prediction of alcohol disorders in early adulthood: a birth cohort study. Arch Gen Psychiatry. 2006; 63, 10091016.
5. Hannigan, JH, Chiodo, LM, Sokol, RJ, Janisse, J, Delaney-Black, V. Prenatal alcohol exposure selectively enhances young adult perceived pleasantness of alcohol odors. Physiol Behav. 2015; 148, 7177.
6. Miranda-Morales, RS, Nizhnikov, ME, Spear, NE. Prenatal exposure to ethanol during late gestation facilitates operant self-administration of the drug in 5-day-old rats. Alcohol. 2014; 48, 1923.
7. Fabio, MC, Macchione, AF, Nizhnikov, ME, Pautassi, RM. Prenatal ethanol increases ethanol intake throughout adolescence, alters ethanol-mediated aversive learning, and affects mu but not delta or kappa opioid receptor mRNA expression. Eur J Neurosci. 2015; 41, 15691579.
8. Bordner, K, Deak, T. Endogenous opioids as substrates for ethanol intake in the neonatal rat: the impact of prenatal ethanol exposure on the opioid family in the early postnatal period. Physiol Behav. 2015; 148, 100110.
9. Gangisetty, O, Wynne, O, Jabbar, S, Nasello, C, Sarkar, DK. Fetal alcohol exposure reduces dopamine receptor D2 and increases pituitary weight and prolactin production via epigenetic mechanisms. PLoS One. 2015; 10, e0140699.
10. Gugusheff, JR, Ong, ZY, Muhlhausler, BS. A maternal “junk-food” diet reduces sensitivity to the opioid antagonist naloxone in offspring postweaning. FASEB J. 2013; 27, 12751284.
11. Ong, ZY, Muhlhausler, BS. Maternal “junk-food” feeding of rat dams alters food choices and development of the mesolimbic reward pathway in the offspring. FASEB J. 2011; 25, 21672179.
12. Gardebjer, EM, Anderson, ST, Pantaleon, M, Wlodek, ME, Moritz, KM. Maternal alcohol intake around the time of conception causes glucose intolerance and insulin insensitivity in rat offspring, which is exacerbated by a postnatal high-fat diet. FASEB J. 2015; 29, 26902701.
13. Blizard, DA, Vandenbergh, DJ, Lionikas, A, McClearn, GE. Learning in the 2-bottle alcohol preference test. Alcohol Clin Exp Res. 2008; 32, 20412046.
14. Phillips, TJ, Brown, KJ, Burkhart-Kasch, S, et al. Alcohol preference and sensitivity are markedly reduced in mice lacking dopamine D2 receptors. Nat Neurosci. 1998; 1, 610615.
15. Werts, RL, Van Calcar, SC, Wargowski, DS, Smith, SM. Inappropriate feeding behaviors and dietary intakes in children with fetal alcohol spectrum disorder or probable prenatal alcohol exposure. Alcohol Clin Exp Res. 2014; 38, 871878.
16. Cullere, ME, Spear, NE, Molina, JC. Prenatal ethanol increases sucrose reinforcement, an effect strengthened by postnatal association of ethanol and sucrose. Alcohol. 2014; 48, 2533.
17. Dalle Molle, R, Laureano, DP, Alves, MB, et al. Intrauterine growth restriction increases the preference for palatable foods and affects sensitivity to food rewards in male and female adult rats. Brain Res. 2015; 1618, 4149.
18. Yusuf, F, Leeder, SR. Making sense of alcohol consumption data in Australia. Med J Aust. 2015; 203, 128130, 130e.121.
19. Bellinger, L, Lilley, C, Langley-Evans, SC. Prenatal exposure to a maternal low-protein diet programmes a preference for high-fat foods in the young adult rat. Br J Nutr. 2004; 92, 513520.
20. Gugusheff, JR, Bae, SE, Rao, A, et al. Sex and age-dependent effects of a maternal junk food diet on the µ-opioid receptor in rat offspring. Behav Brain Res. 2016; 301, 124131.
21. Arias, C, Chotro, MG. Increased palatability of ethanol after prenatal ethanol exposure is mediated by the opioid system. Pharmacol Biochem Behav. 2005; 82, 434442.
22. Matta, R, Tiessen, AN, Choleris, E. The role of dorsal hippocampal dopamine D1-type receptors in social learning, social interactions, and food intake in male and female mice. Neuropsychopharmacology. 2017; [Epub ahead of print].
23. Galaj, E, Manuszak, M, Arastehmanesh, D, Ranaldi, R. Microinjections of a dopamine D1 receptor antagonist into the ventral tegmental area block the expression of cocaine conditioned place preference in rats. Behav Brain Res. 2014; 272, 279285.
24. Seney, ML, Ekong, KI, Ding, Y, Tseng, GC, Sibille, E. Sex chromosome complement regulates expression of mood-related genes. Biol Sex Differ. 2013; 4, 20.
25. Gardebjer, EM, Cuffe, JS, Pantaleon, M, Wlodek, ME, Moritz, KM. Periconceptional alcohol consumption causes fetal growth restriction and increases glycogen accumulation in the late gestation rat placenta. Placenta. 2014; 35, 5057.
26. Bellinger, L, Sculley, DV, Langley-Evans, SC. Exposure to undernutrition in fetal life determines fat distribution, locomotor activity and food intake in ageing rats. Int J Obes. 2006; 30, 729738.
27. Joss-Moore, LA, Wang, Y, Campbell, MS, et al. Uteroplacental insufficiency increases visceral adiposity and visceral adipose PPARgamma2 expression in male rat offspring prior to the onset of obesity. Early Hum Dev. 2010; 86, 179185.
28. Gugusheff, J, Sim, P, Kheng, A, et al. The effect of maternal and post-weaning low and high glycaemic index diets on glucose tolerance, fat deposition and hepatic function in rat offspring. J Dev Orig Health Dis. 2016; 7, 320329.
29. Barr, HM, Bookstein, FL, O’Malley, KD, et al. Binge drinking during pregnancy as a predictor of psychiatric disorders on the Structured Clinical Interview for DSM-IV in young adult offspring. Am J Psychiatry. 2006; 163, 10611065.
30. Famy, C, Streissguth, AP, Unis, AS. Mental illness in adults with fetal alcohol syndrome or fetal alcohol effects. Am J Psychiatry. 1998; 155, 552554.
31. Streissguth, AP, Bookstein, FL, Barr, HM, et al. Risk factors for adverse life outcomes in fetal alcohol syndrome and fetal alcohol effects. JDBP. 2004; 25, 228238.
32. Knee, DS, Sato, AK, Uyehara, CFT, Claybaugh, JR. Prenatal exposure to ethanol causes partial diabetes insipidus in adult rats. Am J Physiol I. 2004; 287, R277R283.


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The impact of periconceptional alcohol exposure on fat preference and gene expression in the mesolimbic reward pathway in adult rat offspring

  • E. S. Dorey (a1), C. L. Cullen (a1) (a2), D. Lucia (a1), K. M. Mah (a1), M.-L. Roy Manchadi (a1), B. S. Muhlhausler (a3) and K. M. Moritz (a1) (a4)...


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