Ritalin may cause long-lasting changes in brain-cell function, UB resear...( riatum a brain structure important for...)

riatum, a brain structure important for both movement and motivation, and the presence of c-fos activity there has been implicated in the mechanism of addiction, Baizer said. The researchers wanted to see if methylphenidate caused c-fos activation in the same parts of the brain, and at the same levels, as the other drugs.

Using young rats as an animal model, they gave one group sweetened milk containing a relatively high dose of methylphenidate (20 mg/kg). Considering the differences in metabolism between rats and humans, this is comparable approximately to a dose on the high end of the range that is used therapeutically, Baizer said. They administered the drug at a time during the rat's 24-hour cycle that would simulate the timing of a child's dose. Another group received just sweetened milk. After 90 minutes, the optimal time for c-fos development in brain cells, the brains of both groups were analyzed for the presence of c-fos.

Results showed there were many more neurons with c-fos activity in the brains of rats given methylphenidate, particularly in the striatum, Baizer said, than in the brains of control rats. Rats receiving no treatment and sacrificed after a period of rest showed still less c-fos activity, suggesting that some of the c-fos activity is related to moving around in the home cage and not a pure drug effect.

"These data do suggest that there are effects of Ritalin on cell function that outlast the short term and we should sort that out," Baizer said. "There is no indication of tolerance, but we have no idea if there is adaptation to the effects."

One next step, she said, is to use microarray technology to see what other genes are turned on in response to short and long-term Ritalin use. Additional researchers on the study were Ashley Acheson, a graduate student in the UB Department of Psychology; Alexis Thompson, Ph.D., a research scientist at the UB Research Institute on Addictions, and Mark B. Kristal, Ph.D., UB
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Contact: Lois Baker
ljbaker@buffalo.edu
716-645-5000 x 1417
University at Buffalo
11-Nov-2001

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