Original articleMethylphenidate Preferentially Increases Catecholamine Neurotransmission within the Prefrontal Cortex at Low Doses that Enhance Cognitive Function
Section snippets
Animals and Surgery
Male Sprague-Dawley rats (290–370 g; Charles River, Wilmington, Massachusetts) had ad libitum access to food and water. For microdialysis testing, a microdialysis probe was lowered into the PFC (A+3.2; L1.0; V-5.0 at an angle of 4° lateral), the core subregion of the ACC (A+1.7; L1.4; V-7.8), or the MSA (A-.7; L.5; V-7.8) on the day before testing, as described previously (Berridge and Stalnaker 2002). Electroencephalographic and electromyographic electrodes were implanted, as described below.
Plasma Levels of MPH after Oral and IP Administration
Clinically, psychostimulants are administered orally and exert therapeutic actions at low doses when plasma concentrations are within the range of 8–40 ng/mL (Swanson and Volkow 2001). Previous studies estimated that similar plasma levels are obtained in rats after oral administration of 1.0–3.0 mg/kg (Kuczenski and Segal 2002). We obtained similar results with orally administered MPH at a dose of 2.0 mg/kg (n = 7), which resulted in plasma levels of 22 ± 7 ng/mL 15 min after drug
Overview of Results
Despite the widespread use of low-dose psychostimulants in the treatment of ADHD, surprisingly little is known about the neural mechanisms that underlie the therapeutic actions of these drugs. The current studies provide the novel observation that, when administered at low-doses that enhance cognitive function, MPH preferentially activates DA and NE efflux within the PFC relative to subcortical regions. Moreover, the effect of low-dose MPH on NE efflux within the MSA was comparable to that
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