University of Massachusetts Medical School Faculty Publications
Title
VTA CRF neurons mediate the aversive effects of nicotine withdrawal and promote intake escalation
UMMS Affiliation
Brudnick Neuropsychiatric Research Institute, Department of Psychiatry; Tapper Lab
Publication Date
12-2014
Document Type
Article
Disciplines
Neuroscience and Neurobiology
Abstract
Dopaminergic neurons in the ventral tegmental area (VTA) are well known for mediating the positive reinforcing effects of drugs of abuse. Here we identify in rodents and humans a population of VTA dopaminergic neurons expressing corticotropin-releasing factor (CRF). We provide further evidence in rodents that chronic nicotine exposure upregulates Crh mRNA (encoding CRF) in dopaminergic neurons of the posterior VTA, activates local CRF1 receptors and blocks nicotine-induced activation of transient GABAergic input to dopaminergic neurons. Local downregulation of Crh mRNA and specific pharmacological blockade of CRF1 receptors in the VTA reversed the effect of nicotine on GABAergic input to dopaminergic neurons, prevented the aversive effects of nicotine withdrawal and limited the escalation of nicotine intake. These results link the brain reward and stress systems in the same brain region to signaling of the negative motivational effects of nicotine withdrawal.
Keywords
Addiction, Reward
DOI of Published Version
10.1038/nn.3872
Source
Nat Neurosci. 2014 Dec;17(12):1751-8. doi: 10.1038/nn.3872. Epub 2014 Nov 17. Link to article on publisher's site
Related Resources
Journal/Book/Conference Title
Nature neuroscience
PubMed ID
25402857
Repository Citation
Grieder, Taryn E.; Tapper, Andrew R.; and George, Olivier, "VTA CRF neurons mediate the aversive effects of nicotine withdrawal and promote intake escalation" (2014). University of Massachusetts Medical School Faculty Publications. 1463.
https://escholarship.umassmed.edu/faculty_pubs/1463
Comments
Full author list omitted for brevity. For the full list of authors, see article.