| Literature DB >> 25402857 |
Taryn E Grieder1, Melissa A Herman2, Candice Contet2, Laura A Tan3, Hector Vargas-Perez1, Ami Cohen2, Michal Chwalek1, Geith Maal-Bared1, John Freiling2, Joel E Schlosburg2, Laura Clarke1, Elena Crawford2, Pascale Koebel4, Vez Repunte-Canonigo5, Pietro P Sanna5, Andrew R Tapper6, Marisa Roberto2, Brigitte L Kieffer7, Paul E Sawchenko3, George F Koob8, Derek van der Kooy1, Olivier George2.
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.Entities:
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Year: 2014 PMID： 25402857 PMCID： PMC4241147 DOI： 10.1038/nn.3872
Source DB: PubMed Journal: Nat Neurosci ISSN： 1097-6256 Impact factor: 24.884