Dr. Susan L. Andersen and colleagues at Harvard Medical School and McLean Hospital in Belmont, Massachusetts treated pre-adolescent rats with two daily injections of methylphenidate or with vehicle at ages 20 to 35 days. The investigators looked at how much time the adult rats spent in locations they had been conditioned to associate with a cocaine «reward.»

The methylphenidate-treated rats spent less time in such areas, «suggesting aversion to cocaine,» the researchers report in the online December 3rd edition of Nature Neuroscience. In addition, the animals exhibited decreases in the locomotor-activating effects of cocaine.

The levels of the transcription factor cAMP response element binding protein (CREB) were 50% higher in the nucleus accumbens methylphenidate-exposed rats. Such CREB activity has been linked to decreases in the reward response to cocaine.

In a separate experiment, adult rats that received methylphenidate were also less likely to congregate in cocaine-associated areas. However, unlike the animals treated at a younger age, they showed a normal response to the stimulating effects of cocaine.

The animals treated during adulthood also showed increased CREB activity, but it was accompanied by elevated levels of a protein called GluR2. According to Dr. Andersen, this suggests the balance between the two might be important in sensitivity to cocaine.

In an interview, Dr. Andersen said that while these findings could suggest stimulant treatment for ADHD decreases the likelihood of later cocaine abuse, the phenomenon occurred in rats and these rats were considered to be «normal.» Therefore, a person affected by ADHD may have a different drug response altogether, she noted.

In addition, Dr. Andersen pointed out, it is possible that early stimulant exposure could blunt a persons response to other, normally pleasurable experiences. The basic pleasures such as food and sex have been shown to affect the same «reward centers» in the brain that illegal drugs do.

Dr. Nancy Pilotte of the National Institute on Drug Abuse in Bethesda, Maryland, agreed that there is a lack of data on any long-term brain changes methylphenidate use might induce.

Nevertheless, Dr. Pilotte is «excited» about the current findings, and pointed out that they mirror recent research linking methylphenidate use to a lower risk of substance abuse among children with ADHD.