title: Muscarinic, but not nicotinic, acetylcholine receptor blockade in the ventral tegmental area attenuates cue-induced sucrose-seeking.
abstract: The mesolimbic dopamine (DA) system is known to play a role in cue-mediated reward-seeking for natural rewards and drugs of abuse. Specifically, cholinergic and glutamatergic receptors in the ventral tegmental area (VTA) have been shown to regulate cue-induced drug-seeking. However, the potential role of these VTA receptors in regulating cue-induced reward seeking for natural rewards is unknown. Here, we examined whether blockade of VTA acetylcholine receptors (AChRs) and N-methyl-d-aspartate receptors (NMDARs) would alter cue-induced sucrose seeking in male Sprague-Dawley rats. Subjects underwent 10 days of sucrose self-administration training (fixed ratio 1 schedule) followed by 7 days of forced abstinence. On withdrawal day 7, rats received bilateral VTA infusion of vehicle, the muscarinic AChR antagonist scopolamine (2.4 or 24 μg/side), the nicotinic AChR antagonist mecamylamine (3 or 30 μg/side), or the NMDAR antagonist AP-5 (0.1 or 1 μg/side) immediately prior to examination of cue-induced sucrose-seeking. Scopolamine infusion led to robust attenuation, but did not completely block, sucrose-seeking behavior. In contrast, VTA administration of mecamylamine or AP-5 did not alter cue-induced sucrose-seeking. Together, the data suggest that VTA muscarinic AChRs, but not nicotinic AChRs nor NMDARs, facilitate the ability of food-associated cues to drive seeking behavior for a food reward.
authors.affiliation: Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT 06511, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA; Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06511, USA. Electronic address: nii.addy@yale.edu.
authors.forename: Nii A
authors.initials: NA
authors.lastname: Addy
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Nunes
authors.affiliation: Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT 06511, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wickham
mesh_terms: D000818:Animals; D001070:Appetitive Behavior / Q000187:drug effects* / Q000502:physiology; D015331:Cohort Studies; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D003463:Cues; D019422:Dietary Sucrose / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009042:Motivation / Q000187:drug effects / Q000502:physiology; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009483:Neuropsychological Tests; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D012201:Reward; D012601:Scopolamine / Q000494:pharmacology; D012646:Self Administration; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism
chemical_list: D019422:Dietary Sucrose; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D008464:Mecamylamine; D012601:Scopolamine
keywords: Mecamylamine; Mesolimbic dopamine system; NMDA receptor; Reward-seeking behavior; Scopolamine