( ntists have learned little about how AD...)Study reveals how ADHD drugs work in brain

"It is surprising that no one was looking at low-dose [ADHD] drugs because we know that the drugs are most effective only at low doses," says Berridge. "So we asked the natural question: what are these drugs doing at clinically relevant doses?"

To answer that question, Berridge and his team monitored neurotransmitter levels in three different brain regions thought to be targeted by ADHD drugs: the PFC and two smaller brain areas known as the accumbens which has been linked with processing "rewards," and the medial septum, which has been implicated in arousal and movement.

Working with rats, the researchers conducted laboratory and behavioral tests to ensure that animal drug doses were functionally equivalent to doses prescribed in humans. Then, using a type of brain probe - a process known as microdialysis - the UW-Madison team measured concentrations of dopamine and norepinephrine in the three different brain areas, both in the presence and absence of low-dose ADHD stimulants.

Under the influence of ADHD drugs, dopamine and norepinephrine levels increased in the rats' PFC. Levels in the accumbens and medial septum, however, remained much the same, the scientists found.

"Our work provides pretty important information on the importance of targeting the PFC when treating ADHD," says Berridge, "In particular it tells us that if we want to produce new ADHD drugs, we need to target [neurotransmitter] transmission in the PFC."

In the future, Berridge and his colleagues plan to look deeper within the PFC to gain more detailed insights into how ADHD meds act on nerves to enhance cognitive ability.

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Source:University of Wisconsin-Madison