Rewarding, reinforcing and incentive salient events involve orexigenic hypothalamic neuropeptides regulating mesolimbic dopaminergic neurotransmission.
The hypothalamus is an integrated energy sensing system interfacing with higher motivational structures of the mesocorticolimbic dopamine (DA) system. This interconnectivity is strictly regulated by a number of orexigenic hypothalamic neuropeptides, including especially ghrelin, orexins and neuropeptide Y (NPY), enabling the latter to modulate salient events of natural and chemical reinforcers. In this review we aim to analyse the current knowledge on these three orexigenic neuropeptide systems that are involved in the DAergic regulation of psychostimulant behaviours. We will first review the co-existing interactions between ghrelin, orexins and NPY in hypothalamic nuclei. We will next outline whether these neuropeptides can affect DAergic neurotransmission by either regulating the firing rate of DA neurons in the ventral tegmental area (VTA) or by presynaptically interacting on the DAergic nerve terminals. Finally, we will underscore the main studies that outlined the involvement of ghrelin, orexins and NPY with rewarding, reinforcing and incentive properties of natural reinforcers and drugs of abuse. The reciprocal hypothalamic interaction of ghrelin, orexins and NPY might represent a new central view on neuronal mechanisms regulating the behavioural phenomenology of addiction maintained by the DA system.
Center for Neurosciences C4N, Vrije Universiteit Brussel, Faculty of Medicine and Pharmacy, Department FASC, Laarbeeklaan 103, 1090 Brussels, Belgium. Electronic address: dquarta@bnc-group.com.
Davide
D
Quarta
Center for Neurosciences C4N, Vrije Universiteit Brussel, Faculty of Medicine and Pharmacy, Department FASC, Laarbeeklaan 103, 1090 Brussels, Belgium. Electronic address: Ilse.Smolders@vub.ac.be.
Ilse
I
Smolders
D000818:Animals; D016739:Behavior, Addictive; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000378:metabolism*; D055030:Drug Users / Q000523:psychology; D054439:Ghrelin / Q000378:metabolism; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism* / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008032:Limbic System / Q000378:metabolism / Q000503:physiopathology; D009042:Motivation; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology; D009478:Neuropeptide Y / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D000068797:Orexins; D012054:Reinforcement, Psychology; D012201:Reward; D019966:Substance-Related Disorders / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology*; D009435:Synaptic Transmission
D054439:Ghrelin; D047908:Intracellular Signaling Peptides and Proteins; D009478:Neuropeptide Y; D009479:Neuropeptides; D000068797:Orexins; D004298:Dopamine
Dopamine; Drugs of abuse; Ghrelin; Neuropeptide Y; Orexin