Document Detail


Intermittent nicotine exposure upregulates nAChRs in VTA dopamine neurons and sensitises locomotor responding to the drug.
MedLine Citation:
PMID:  23331514     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Dopaminergic projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAcc) mediate the behavioral and motivational effects of many drugs of abuse, including nicotine. Repeated intermittent administration of these drugs, a pattern often associated with initial drug exposure, sensitises the reactivity of dopamine (DA) neurons in this pathway, enhances the locomotor behaviors the drugs emit, and promotes their pursuit and self-administration. Here we show that activation of nicotinic acetylcholine receptors (nAChRs) in the VTA, but not the NAcc, is essential for the induction of locomotor sensitisation by nicotine. Repeated intermittent nicotine exposure (4 × 0.4 mg/kg, base, i.p., administered over 7 days), a regimen leading to long-lasting locomotor sensitisation, also produced upregulation of nAChRs in the VTA, but not the NAcc, in the hours following the last exposure injection. Functional nAChR upregulation was observed selectively in DA but not GABA neurons in the VTA. These effects were followed by long-term potentiation of excitatory inputs to these cells and increased nicotine-evoked DA overflow in the NAcc. Withdrawal symptoms were not observed following this exposure regimen. Thus, intermittent activation and upregulation by nicotine of nAChRs in DA neurons in the VTA may contribute to the development of behavioral sensitisation and increased liability for nicotine addiction.
Authors:
Lorinda K Baker; Danyan Mao; Henry Chi; Anitha P Govind; Yolanda F Vallejo; Michael Iacoviello; Stacy Herrera; James J Cortright; William N Green; Daniel S McGehee; Paul Vezina
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-01-21
Journal Detail:
Title:  The European journal of neuroscience     Volume:  37     ISSN:  1460-9568     ISO Abbreviation:  Eur. J. Neurosci.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-19     Completed Date:  2013-08-29     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  8918110     Medline TA:  Eur J Neurosci     Country:  France    
Other Details:
Languages:  eng     Pagination:  1004-11     Citation Subset:  IM    
Copyright Information:
© 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.
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MeSH Terms
Descriptor/Qualifier:
Animals
Central Nervous System Sensitization
Dopamine / metabolism
Dopaminergic Neurons / drug effects,  metabolism,  physiology*
GABAergic Neurons / metabolism
Locomotion / drug effects*
Long-Term Potentiation / drug effects
Male
Nicotine / pharmacology*
Nicotinic Agonists / pharmacology*
Nucleus Accumbens / metabolism,  physiology
Rats
Rats, Sprague-Dawley
Receptors, Nicotinic / drug effects,  metabolism*
Up-Regulation
Ventral Tegmental Area / cytology,  metabolism,  physiology*
Grant Support
ID/Acronym/Agency:
P01 DA019695/DA/NIDA NIH HHS; P01 DA019695/DA/NIDA NIH HHS; R01 DA015918/DA/NIDA NIH HHS; R01 DA015918/DA/NIDA NIH HHS; R01 NS043782/NS/NINDS NIH HHS; R01 NS043782/NS/NINDS NIH HHS; T32 DA007255/DA/NIDA NIH HHS; T32 DA07255/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Nicotinic Agonists; 0/Receptors, Nicotinic; 54-11-5/Nicotine; VTD58H1Z2X/Dopamine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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