Journal
NATURE NEUROSCIENCE
Volume 17, Issue 12, Pages 1751-1758Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.3872
Keywords
-
Categories
Funding
- Canadian Institutes of Health Research
- US National Institute on Drug Abuse [DA023597, DA035371, DA031566]
- US National Institute on Alcohol Abuse and Alcoholism [AA021491, AA015566, F32 AA020430, AA006420, AA016658, AA021667, INIA AA013498]
- Tobacco-Related Disease Research Program [12RT-0099]
- US National Institute of Diabetes and Digestive and Kidney Diseases [DK026741]
- Clayton Medical Research Foundation
Ask authors/readers for more resources
Dopaminergic neurons in the ventral tegmental area (VIA) are well known for mediating the positive reinforcing effects of drugs of abuse. Here we identify in rodents and humans a population of VIA 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 VIA, 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 VIA 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available
Share Paper
