Methylphenidate DAT binding in adolescents with Attention-Deficit/ Hyperactivity Disorder comorbid with Substance Use Disorder--a single photon emission computed tomography with [Tc(99m)]TRODAT-1 study.

BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is highly prevalent among adolescents with Substance Use Disorders (SUD). Effects of methylphenidate (MPH) on ADHD are attributed to its properties of blocking the dopamine transporter (DAT) in the striatum. However, it has been demonstrated that drug addiction is associated with dopaminergic system changes that may affect MPH brain effects, emphasizing the need to better understand MPH actions in subjects with ADHD+SUD. OBJECTIVES: To evaluate the effect of an extended release formulation of MPH (MPH-SODAS) on DAT availability in 17 stimulant-naive ADHD adolescents with comorbid SUD (cannabis and cocaine). METHODS: Subjects underwent two single photon emission computed tomography (SPECT) scans with [Tc(99m)]TRODAT-1, at baseline and after 3 weeks on MPH-SODAS. Clinical assessment for ADHD relied on the Swanson, Nolan and Pelham Scale - version IV (SNAP-IV). Caudate and putamen DAT binding potential (BP) was calculated. RESULTS: After 3 weeks on MPH-SODAS, there was a significant reduction of SNAP-IV total scores (p<0.001), and approximately 52% reductions of DAT BP at the left and right caudate. Similar decreases were found at the left and right putamen (p<0.001 for all analyses). DISCUSSION: This study shows that the magnitude of DAT blockade induced by MPH in this population is similar to what is found in ADHD patients without SUD comorbidity, providing neurobiological support for trials with stimulants in adolescents with ADHD+SUD, an important population excluded from studies.

Antioxidant enzyme activities following acute or chronic methylphenidate treatment in young rats.

Methylphenidate (MPH) is psychostimulants used to treat Attention-Deficit/Hyperactivity Disorder and can lead to a long-lasting neurochemical and behavioral adaptations in experimental animals. In the present study, the cerebral antioxidant enzymatic system, superoxide dismutase (SOD) and catalase (CAT) was evaluated at in different age following MPH (1, 2 or 10 mg/kg MPH, i.p.) treatment in young rats. In the acute treatment the SOD activity decreased in the cerebral prefrontal cortex with opposite effect in the cerebral cortex; and the CAT activity decreased in hippocampus. In the chronic treatment the SOD activity increased in the hippocampus and cerebral cortex and decreased in the striatum. The observed changes on the enzyme activities in rat brain were dependent on the structure brain region and duration of treatment with MPH. Probably, the activity of enzymes was not be enough to prevent MPH-induced oxidative damage in specific regions from brain, such as observed for us in another recent study.