Here, we determined the effects of chronic methylphenidate (MPH) treatment on brain dopamine (DA) systems, developmental milestones, and later vulnerability to substance abuse in juvenile nonhuman primates. Male rhesus monkeys (approximately 30 months old) were treated daily with either a sustained release formulation of MPH or placebo (N = 8 per group). Doses were titrated to achieve initial drug blood serum levels within the therapeutic range in children and

adjusted throughout the study to maintain target levels. Growth, including measures of crown-rump length and weight, was assessed before and after 1 year of treatment and after 3-5 months selleck chemicals llc washout. In addition, positron emission tomography scans were performed to quantify binding availability of D2/D3 receptors and dopamine transporters (DATs). Distribution volume ratios were calculated to quantify binding of [F-18]fluoroclebopride (DA D2/D3) and [F-18]-(+)-N-(4-fluorobenzyl)-2 beta-propanoyl-3 beta-(4-chlorophenyl) tropane (DAT). Chronic MPH did not differentially alter the course of weight gain or other GSK2118436 concentration measures of growth, nor did it influence DAT or D2/D3 receptor availability after 1 year of treatment. However, after washout, the D2/D3 receptor availability of MPH-treated animals did not continue to decline at the

same rate as control animals. Acquisition of intravenous cocaine self-administration was examined by first substituting saline

for food reinforcement and then cocaine doses (0.001-0.1 mg/kg per injection) in ascending order. Each dose was available for at least five consecutive sessions. The lowest dose Flavopiridol (Alvocidib) of cocaine that maintained response rates significantly higher than saline-contingent rates was operationally defined as acquisition of cocaine reinforcement. There were no differences in rates of acquisition, overall response rates, or cocaine intake as a function of cocaine dose between groups. In an animal model that closely mimics human development; chronic treatment with therapeutic doses of sustained release MPH did not have a significant influence on the regulation of DATs or D2/D3 receptors, or on standard measures of growth. Furthermore, this treatment regimen and subsequent drug washout did not have an impact on vulnerability to cocaine abuse. Neuropsychopharmacology (2012) 37, 2555-2565; doi:10.1038/npp.2012.117; published online 18 July 2012″
“Background. Despite the growing recognition that the clinical symptom characteristics associated with attention deficit hyperactivity disorder (ADHD) persist into adulthood in a high proportion of subjects, little is known about the persistence of neurocognitive deficits in ADHD.