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Biol Psychiatry. 2006 Nov 15;60(10):1111-20. Epub 2006 Jun 23.

Methylphenidate preferentially increases catecholamine neurotransmission within the prefrontal cortex at low doses that enhance cognitive function.

Author information

1
Psychology Department, University of Wisconsin, Madison, WI 53706, USA. Berridge@wisc.edu

Abstract

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.

PMID:
16806100
DOI:
10.1016/j.biopsych.2006.04.022
[Indexed for MEDLINE]

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