Document Detail


Neurocircuitry underlying the preferential sensitivity of prefrontal catecholamines to low-dose psychostimulants.
MedLine Citation:
PMID:  23303075     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Low doses of psychostimulants, including methylphenidate (MPH), are highly effective in the treatment of attention-deficit/hyperactivity disorder (ADHD). At these doses, psychostimulants improve prefrontal cortex (PFC)-dependent function. Recent evidence indicates that low and clinically relevant doses of psychostimulants target norepinephrine (NE) and dopamine (DA) signaling preferentially in the PFC. To better understand the neural mechanisms responsible for the regional selectivity of low-dose psychostimulant action, it is important to first identify the underlying neurocircuitry. The current study used reverse microdialysis to test the hypothesis that the preferential targeting of PFC catecholamines by low-dose psychostimulants involves direct action within the PFC, reflecting an intrinsic property of this region. For these studies, the effects of varying concentrations of MPH (0.25, 1.0, and 4.0 μM) on NE and DA efflux were examined within the PFC and select subcortical fields in unanesthetized rats. Low concentrations of MPH elicited significantly larger increases in extracellular levels of NE and DA in the PFC than in subcortical regions linked to motor-activating and arousal-promoting actions of psychostimulants (nucleus accumbens and medial septal area, respectively). The differential action of MPH across regions disappeared at higher concentrations. The enhanced sensitivity of PFC catecholamines to low and clinically relevant doses of psychostimulants, at least in part, reflects a unique sensitivity of this region to NE/DA transporter blockade. Available evidence suggests that the increased sensitivity of PFC catecholamines likely involves DA clearance through the NE transporter within the PFC.
Authors:
Brooke E Schmeichel; Craig W Berridge
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-02-06
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  38     ISSN:  1740-634X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-16     Completed Date:  2014-01-21     Revised Date:  2014-05-07    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  England    
Other Details:
Languages:  eng     Pagination:  1078-84     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Catecholamines / metabolism*
Central Nervous System Stimulants / administration & dosage*
Dose-Response Relationship, Drug
Male
Microdialysis / methods
Nerve Net / drug effects*,  metabolism*
Prefrontal Cortex / drug effects*,  metabolism*
Rats
Rats, Sprague-Dawley
Grant Support
ID/Acronym/Agency:
MH081843/MH/NIMH NIH HHS; R01 MH081843/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Catecholamines; 0/Central Nervous System Stimulants
Comments/Corrections

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