Attention-Deficit Hyperactivity Disorder (ADHD) is a widespread condition with variable underlying causes. A common therapeutic, called methylphenidate, seeks to treat symptoms of ADHD by moderating the brain's dopamine level which is a neurotransmitter involved reward systems. But, the exact mechanism to how methylphenidate works remains largely understood.
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"We know quite a bit about how methylphenidate works at the molecular level, but not how it affects greater neural systems. It's still a mystery how this drug improves symptoms of ADHD," said Professor Jeff Wickens of Okinawa Institute of Science and Technology Graduate University (OIST)'s Neurobiology Research Unit. "This mystery leads us to explore how different parts of the brain interact to produce therapeutic effects."
To examine its therapeutic effects, researchers investigated the action of the drug in rat models. Researchers used dopamine cell recordings, electrochemical monitoring and computer modeling to bring renewed knowledge on methylphenidate's therapeutic actions in ADHD.
"When you use methylphenidate in the intact brain there's a neural regulation mechanism to compensate for the direct effects of the drug," said Wickens. "Methylphenidate's therapeutic effects could be indirect consequences of this feedback loop."
Findings were published in Progress in Neurobiology and describes how researcher’s administered a concentration of 5.0 mg/kg to a group of adult male rats while the control received no drugs. Researchers first believed that methylphenidate blocks the reuptake of dopamine by receptors in the brain and that should increase the phasic dopamine signal. However, what happened instead was the opposite--methylphenidate decreased the phasic dopamine signal.
Professor Jeff Wickens and technician Kavinda Liyanagama study data from experiments looking at dopamine release in rat brains. Credit: OIST.edu
Computer analysis suggests that methylphenidate mainly affects the tonic dopamine signal and shifts in such signal may improve ADHD symptoms. Researchers are now hopeful to continue their studies in animal models of ADHD and examine feedback loops under such conditions.
Source: Science Daily
