Impact of Early Consumption of High-Fat Diet on the Mesolimbic Dopaminergic System (2017)

F. Naneix, F. Tantot, C. Glangetas, J. Kaufling, Y. Janthakhin, C. Boitard, V. De Smedt-Peyrusse, J. R. Pape, S. Vancassel, P. Trifilieff, F. Georges, E. Coutureau and G. Ferreira

eNeuro 29 May 2017, ENEURO.0120-17.2017;



Increasing evidence suggest that consumption of high-fat diet (HFD) can impact the maturation of brain circuits – such as during adolescence – which could account for behavioral alterations associated with obesity. In the present study, we used behavioral sensitization to amphetamine to investigate the effect of periadolescent HFD exposure (pHFD) in rats on the functionality of the dopamine (DA) system, a central actor in food reward processing. pHFD does not affect responding to an acute injection, however, a single exposure to amphetamine is sufficient to induce locomotor sensitization in pHFD rats. This is paralleled by rapid neurobiological adaptations within the DA system. In pHFD-exposed animals, a single amphetamine exposure induces an increase in bursting activity of DA cells in the ventral tegmental area as well as higher DA release and greater expression of (tyrosine hydroxylase) in the nucleus accumbens (NAc). Post-synaptically, pHFD animals display an increase in NAc D2 receptors and c-Fos expression after amphetamine injection. These findings highlight the vulnerability of DA system to the consumption of HFD during adolescence that may support deficits in reward-related processes observed in obesity.

Significance Statement Consumption of obesogenic diet might impact the development of the reward system, leading to cognitive and behavioral alterations associated with obesity. This study investigates the effects of high-fat diet (HFD) consumption, from childhood to adulthood, on the functionality of mesolimbic dopamine (DA) system using sensitization to amphetamine. We show that a single exposure to amphetamine is sufficient to induce behavioral sensitization in HFD-exposed animals. This is associated with sensitization of the DA mesolimbic pathway, with higher bursting activity of DA neurons and enhanced DA release, greater expression of tyrosine hydroxylase, D2 receptors and c-Fos levels in the NAc. This study demonstrates that early exposure to obesogenic diet consumption alters the sensitivity of DA system that may lead to reward-related disorders.