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flow in the dorsolateral prefrontal cortex and posterior parietal cortex while improving performance of a spatial working memory task. This suggests that cortical networks that normally process spatial working memory become more efficient in response to the drug. Both methylphenidate and amphetamines act by triggering the release of dopamine, norepinephrine, and serotonin, actions mediated via the plasma membrane transporters of these neurotransmitters and via the shared vesicular monoamine transporter (Chapter 6). Based on animal studies with micro-iontophoretic application of selective D1 dopamine receptor agonists (such as the partial agonist SKF38393 or the full agonist SKF81297) and antagonist (such as SCH23390), and clinical evidence in humans with ADHD, it is now believed that dopamine and norepinephrine, but not serotonin, produce the beneficial effects of stimulants on working memory. At abused (relatively high) doses, stimulants can interfere with working memory and cognitive control, as will be discussed below. It is important to recognize, however, that stimulants act not only on working memory function, but also on general levels of arousal and, within the nucleus accumbens, improve the saliency of tasks. Thus, stimulants improve performance on effortful but tedious tasks, probably acting at different sites in the brain through indirect stimulation of dopamine and norepinephrine receptors.
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Therapeutic (relatively low) doses of psychostimulants, such as methylphenidate and amphetamine, improve performance on working memory tasks both in individuals with ADHD and in normal subjects. Positron emission tomography (PET) demonstrates that methylphenidate decreases regional cerebral blood
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Malenka EJ, Nestler SE, Hyman RC (2009). "Chapter 13: Higher
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The mesocortical pathway is shown here in blue, projecting to the prefrontal cortex from the VTA.
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Molecular neuropharmacology: a foundation for clinical neuroscience
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