Therapeutic Doses of Oral Methylphenidate Significantly Increase Extracellular Dopamine in the Human Brain

• DOI: 10.1523/jneurosci.21-02-j0001.2001
• Publication Date: 2018-04-05T15:05:33Z
• Authors: Nora D. Volkow; Gene-Jack Wang; Joanna S. Fowler; Jean Logan; Madina Gerasimov; Laurence Maynard; Yu-Shin Ding; Samuel J. Gatley; Andrew Gifford; Dinko Franceschi
• Keywords: Raclopride

Methylphenidate (Ritalin) is the most commonly prescribed psychoactive drug in children for treatment of attention deficit hyperactivity disorder (ADHD), yet mechanisms responsible its therapeutic effects are poorly understood.Whereas methylphenidate blocks dopamine transporter (main mechanism removal extracellular dopamine), it unclear whether at doses used therapeutically significantly changes (DA) concentration.Here we positron emission tomography and [ 11 C]raclopride (D2 receptor radioligand that competes with endogenous DA binding to receptor) evaluate oral human brain healthy controls.We showed (average dose 0.8 Ϯ 0.11 mg/kg) increased brain, as evidenced by a significant reduction B max /K d (measure D2 availability) striatum (20 12%; p Ͻ 0.0005).These results provide direct evidence within range increases brain.This result coupled recent findings transporters ADHD patients (which expected reductions DA) provides mechanistic framework efficacy methylphenidate.The increase caused blockade predominantly reflects an amplification spontaneously released DA, which turn responsive environmental stimulation.Because decreases background firing rates signal-to-noise target neurons, postulate weak signals subjects would enhance task-specific signaling, improving decreasing distractibility.Alternatively methylphenidate-induced neurotransmitter involved motivation reward, could salience task facilitating "interest elicits" thus performance.