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• W2056432576 endingPage "e49557" @default.
• W2056432576 startingPage "e49557" @default.
• W2056432576 abstract "Ghrelin, an orexigenic peptide, regulates energy balance specifically via hypothalamic circuits. Growing evidence suggest that ghrelin increases the incentive value of motivated behaviours via activation of the cholinergic-dopaminergic reward link. It encompasses the cholinergic afferent projection from the laterodorsal tegmental area (LDTg) to the dopaminergic cells of the ventral tegmental area (VTA) and the mesolimbic dopamine system projecting from the VTA to nucleus accumbens (N.Acc.). Ghrelin receptors (GHS-R1A) are expressed in these reward nodes and ghrelin administration into the LDTg increases accumbal dopamine, an effect involving nicotinic acetylcholine receptors in the VTA. The present series of experiments were undertaken directly to test this hypothesis. Here we show that ghrelin, administered peripherally or locally into the LDTg concomitantly increases ventral tegmental acetylcholine as well as accumbal dopamine release. A GHS-R1A antagonist blocks this synchronous neurotransmitter release induced by peripheral ghrelin. In addition, local perfusion of the unselective nicotinic antagonist mecamylamine into the VTA blocks the ability of ghrelin (administered into the LDTg) to increase N.Acc.-dopamine, but not VTA-acetylcholine. Collectively our data indicate that ghrelin activates the LDTg causing a release of acetylcholine in the VTA, which in turn activates local nicotinic acetylcholine receptors causing a release of accumbal dopamine. Given that a dysfunction in the cholinergic-dopaminergic reward system is involved in addictive behaviours, including compulsive overeating and alcohol use disorder, and that hyperghrelinemia is associated with such addictive behaviours, ghrelin-responsive circuits may serve as a novel pharmacological target for treatment of alcohol use disorder as well as binge eating." @default.
• W2056432576 created "2016-06-24" @default.
• W2056432576 creator A5011345299 @default.
• W2056432576 creator A5062671486 @default.
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• W2056432576 date "2012-11-14" @default.
• W2056432576 modified "2023-10-13" @default.
• W2056432576 title "Concomitant Release of Ventral Tegmental Acetylcholine and Accumbal Dopamine by Ghrelin in Rats" @default.
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• W2056432576 doi "https://doi.org/10.1371/journal.pone.0049557" @default.
• W2056432576 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3498203" @default.
• W2056432576 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23166710" @default.
• W2056432576 hasPublicationYear "2012" @default.
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