Document Detail

Methamphetamine self-administration produces attentional set-shifting deficits and alters prefrontal cortical neurophysiology in rats.
MedLine Citation:
PMID:  21051037     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Chronic methamphetamine abusers exhibit deficits in tasks requiring intact prefrontal cortex function, and prefrontal cortex dysfunction has been implicated in the loss of control over drug use. This study used a combination of behavioral and electrophysiologic assessments in rats with a history of long access methamphetamine self-administration to determine methamphetamine-induced changes in prefrontal cortex-dependent attentional set-shifting performance, drug-seeking, and prefrontal cortex neuronal activity.
METHODS: Male Long-Evans rats self-administered methamphetamine (.02 mg/infusion, intravenous) or received yoked saline infusions for 6 hours a day for 14 days. Cognitive flexibility was assessed using an attentional set-shifting task before 2 weeks of self-administration and 1 day after self-administration. Animals then underwent 11 days of abstinence, followed by three subsequent tests for context-induced drug seeking. Finally, animals were anesthetized, and single-unit in vivo extracellular recordings were performed in the dorsomedial prefrontal cortex.
RESULTS: Methamphetamine-experienced rats showed escalated drug intake and context-induced drug-seeking following abstinence. During the extradimensional set-shift component, meth-experienced rats showed selective impairments that were identical to deficits produced by excitotoxic lesions of the prefrontal cortex. Rats with a history of chronic methamphetamine intake also exhibited higher basal firing frequency and a significantly greater proportion of burst-firing cells in the prefrontal cortex compared with yoked-saline controls.
CONCLUSIONS: Prefrontal cortex-specific alterations in neuronal function may play a key role in methamphetamine-induced attentional deficits and drug-seeking. These data support the possibility that targeting prefrontal cortex pathology may improve treatment outcome in methamphetamine addiction.
Aram Parsegian; W Bailey Glen; Antonieta Lavin; Ronald E See
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-11-03
Journal Detail:
Title:  Biological psychiatry     Volume:  69     ISSN:  1873-2402     ISO Abbreviation:  Biol. Psychiatry     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-04     Completed Date:  2011-04-28     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  0213264     Medline TA:  Biol Psychiatry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  253-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Action Potentials / drug effects,  physiology
Attention / drug effects*
Drug-Seeking Behavior / drug effects
Methamphetamine / administration & dosage,  pharmacology*
Prefrontal Cortex / drug effects,  physiology*
Pyramidal Cells / physiology
Rats, Long-Evans
Self Administration / methods*
Grant Support
C06 RR015455/RR/NCRR NIH HHS; DA014698/DA/NIDA NIH HHS; DA022658/DA/NIDA NIH HHS; P20 DA022658/DA/NIDA NIH HHS; P20 DA022658-01/DA/NIDA NIH HHS; P20 DA022658-02/DA/NIDA NIH HHS; P20 DA022658-03/DA/NIDA NIH HHS; P20 DA022658-04/DA/NIDA NIH HHS; T32D007288//PHS HHS
Reg. No./Substance:

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

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