Related Articles Juvenile methylphenidate modulates reward-related behaviors and cerebral blood flow by decreasing cortical D3 receptors. Eur J Neurosci. 2008 Jun;27(11):2962-72 Authors: Andersen SL, Napierata L, Brenhouse HC, Sonntag KC Attention deficit hyperactivity disorder is associated with reduced cortical blood flow that is reversible with exposure to the psychostimulant methylphenidate (MPH). D3 dopamine receptors modulate stimulant-induced changes in blood flow and are associated with reward processing during young adulthood, but their role in the enduring effects of MPH during development is unknown. Rats were given vehicle (VEH) or MPH (2 mg/kg between postnatal days 20-35) and assessed in young adulthood for regional cerebral blood volume (rCBV) after MPH challenge and mRNA expression levels of dopamine receptors. To probe D3 receptor involvement, juvenile subjects were exposed to VEH, MPH, the D3-preferring agonist +/-7-OHDPAT (0.3 mg/kg), the D3 antagonist nafadotride (Naf; 0.05, 0.5 or 5.0 mg/kg) or a Naf (0.05 mg/kg)/MPH combination, and assessed biochemically and behaviorally. Juvenile MPH exposure increased MPH-induced rCBV in the cingulate and medial prefrontal cortex and thalamus in adulthood. Behaviorally, juvenile MPH- or +/-7-OHDPAT-exposed subjects demonstrated an aversion to cocaine-associated environments, which was prevented by juvenile co-treatment with MPH and Naf, or with adult cortical microinjections of ...
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