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Behav Brain Res. 2015 Sep 15;291:372-6. doi: 10.1016/j.bbr.2015.05.036. Epub 2015 May 28.

Muscarinic, but not nicotinic, acetylcholine receptor blockade in the ventral tegmental area attenuates cue-induced sucrose-seeking.

Author information

1
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.
2
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA.
3
Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT 06511, USA.

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.

KEYWORDS:

Mecamylamine; Mesolimbic dopamine system; NMDA receptor; Reward-seeking behavior; Scopolamine

PMID:
26026787
PMCID:
PMC4497829
DOI:
10.1016/j.bbr.2015.05.036
[Indexed for MEDLINE]
Free PMC Article
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