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Caltech scientists engineer supersensitive receptor, gain better understanding of dopamine system
Date:10/14/2008

ying the genetically modified receptors: because dopamine plays an important role in movement, the mice became quickly and significantly hyperactive. In fact, the researchers note, low doses of nicotine affect mice with these hypersensitive receptors in much the same way that amphetamines affect "normal" mice. Looking more closely at this phenomenon, the researchers write, "could be useful in understanding the causes of human hyperactivity such as that observed in ADHD."

"This technique also gives researchers the power to activate dopamine neurons selectively," says Lester. "We plan to exploit this opportunity to obtain new knowledge about dopamine neurons' functions."

While these sensitized receptors appear on dopamine neurons throughout the brain, the researchers note that they seem to play an especially critical role in what is called the mesolimbic pathway--one of four pathways that control dopamine production throughout the brain, and the one implicated in the addictive properties of drugs like nicotine.

To this end, Lester's team and their collaborators have already begun to explore the possibilities of targeting these receptors with specific drugs that might work to reduce their sensitivity to nicotine, potentially providing a new line of attack for treating nicotine addiction. In fact, notes Drenan, these same drugs might also one day prove useful in treating other dopamine-related conditions, such as ADHD, Parkinson's disease, and schizophrenia.

"By uncovering the biological role of these receptors, especially with regard to their role in the midbrain dopamine system, we show that they are excellent drug targets," says Drenan.


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Contact: Lori Oliwenstein
lorio@caltech.edu
626-395-3631
California Institute of Technology
Source:Eurekalert

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