Background
At low and clinically relevant doses, psychostimulants enhance cognitive and behavioral
function dependent on the prefrontal cortex (PFC) and extended frontostriatal circuitry.
These actions are observed in individuals with attention-deficit/hyperactivity disorder,
as well as in normal human and animal subjects. Despite the widespread use of these
drugs, the sites of action involved in their cognition-enhancing and therapeutic effects
are poorly understood. Indirect and/or correlative evidence suggests the cognition-enhancing/therapeutic
effects of psychostimulants may involve actions directly within the PFC or extended
frontostriatal circuitry. The current studies examined the degree to which methylphenidate
(MPH) (Ritalin) acts within distinct frontostriatal subfields to improve PFC-dependent
cognition as measured in a delayed-response test of spatial working memory.
Methods
Working memory performance was assessed following microinfusion of vehicle or varying
doses of MPH (.03–8.0 μg/500 nL) directly into the dorsomedial PFC (dorsal prelimbic
and dorsal anterior cingulate cortex), the ventromedial PFC (infralimbic), and the
dorsomedial striatum of rats (n = 69).
Results
Methylphenidate infusion into the dorsomedial PFC, but not ventromedial PFC, elicited
an inverted U-shaped facilitation of PFC-dependent cognition as measured in this task.
The magnitude of this improvement was comparable with that seen with systemic administration.
Additional studies demonstrated that although the dorsomedial striatum is necessary
for accurate performance in this task, MPH infusion into this region did not affect
working memory performance.
Conclusions
These observations provide the first definitive evidence that the PFC is a site of
action in the cognition-enhancing and presumably therapeutic actions of low-dose psychostimulants.
Key Words
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Article info
Publication history
Published online: January 03, 2012
Accepted:
December 2,
2011
Received in revised form:
November 18,
2011
Received:
October 6,
2011
Identification
Copyright
© 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
