Impact of Early Consumption of High-Fat Diet on the Mesolimbic Dopaminergic System.

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 (VTA) as well as higher DA release and greater expression of (tyrosine hydroxylase, TH) 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.

The antero-posterior heterogeneity of the ventral tegmental area.

The ventral tegmental area (VTA) is a brain region processing salient sensory and emotional information, controlling motivated behaviors, natural or drug-related reward, reward-related learning, mood, and participating in their associated psychopathologies. Mostly studied for its dopamine neurons, the VTA also includes functionally important GABA and glutamate cell populations. Behavioral evidence supports the presence of functional differences between the anterior VTA (aVTA) and the posterior VTA (pVTA), which is the topic of this review. This antero-posterior heterogeneity concerns locomotor activity, conditioned place preference and intracranial self-administration, and can be seen in response to ethanol, acetaldehyde, salsolinol, opioids including morphine, cholinergic agonists including nicotine, cocaine, cannabinoids and after local manipulation of GABA and serotonin receptors. It has also been observed after viral-mediated manipulation of GluR1, phospholipase Cγ (PLCγ) and cAMP response element binding protein (CREB) expression, with impact on reward and aversion-related responses, on anxiety and depression-related behaviors and on pain sensitivity. In this review, the substrates potentially underlying these aVTA/pVTA differences are discussed, including the VTA sub-nuclei and the heterogeneity in connectivity, cell types and molecular characteristics. We also review the role of the tail of the VTA (tVTA), or rostromedial tegmental nucleus (RMTg), which may also participate to the observed antero-posterior heterogeneity of the VTA. This region, partly located within the pVTA, is an inhibitory control center for dopamine activity. It controls VTA and substantia nigra dopamine cells, thus exerting a major influence on basal ganglia functions. This review highlights the need for a more comprehensive analysis of VTA heterogeneity.