Background
Low doses of psychostimulants, such as methylphenidate (MPH), are widely used in the
treatment of attention-deficit/hyperactivity disorder (ADHD). Surprisingly little
is known about the neural mechanisms that underlie the behavioral/cognitive actions
of these drugs. The prefrontal cortex (PFC) is implicated in ADHD. Moreover, dopamine
(DA) and norepinephrine (NE) are important modulators of PFC-dependent cognition.
To date, the actions of low-dose psychostimulants on PFC DA and NE neurotransmission
are unknown.
Methods
In vivo microdialysis was used to compare the effects of low-dose MPH on NE and DA
efflux within the PFC and select subcortical fields in male rats. Doses used (oral,
2.0 mg/kg; intraperitoneal, .25–1.0 mg/kg) were first determined to produce clinically
relevant plasma concentrations and to facilitate both PFC-dependent attention and
working memory.
Results
At low doses that improve PFC-dependent cognitive function and that are devoid of
locomotor-activating effects, MPH substantially increases NE and DA efflux within
the PFC. In contrast, outside the PFC these doses of MPH have minimal impact on NE
and DA efflux.
Conclusions
The current observations suggest that the therapeutic actions of low-dose psychostimulants
involve the preferential activation of catecholamine neurotransmission within the
PFC.
Key Words
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Article info
Publication history
Published online: June 24, 2006
Accepted:
April 26,
2006
Received in revised form:
April 25,
2006
Received:
March 2,
2006
Identification
Copyright
© 2006 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
