Parents, doctors, and others have wondered whether common treatments for attention-deficit hyperactivity disorder (ADHD) inadvertently predispose adolescents to future drug abuse.
The answer may depend on the age at which treatment is started and how long it lasts, say the authors of a new brain-imaging and behavioral study conducted in animals at the U.S. Department of Energy's Brookhaven National Laboratory. The results appear in the June 5, 2007 online issue of the journal Pharmacology, Biochemistry and Behavior.
"Our study shows that the brain's reward pathways are definitely influenced by methylphenidate, one of the stimulant drugs commonly used to treat ADHD," said Brookhaven researcher Panayotis (Peter) Thanos, lead author of the study. "But the brain chemistry changes we observed suggest that the developmental stage at which treatment begins and the duration of treatment are important variables that need further study."
In the study, rats were given methylphenidate mixed with distilled water beginning one month after birth -- early adolescence for rats. Animals received either 1 or 2 milligrams methylphenidate per kilogram of body weight, consistent with clinical doses given to children with ADHD. A control group of rats was handled under identical conditions but given plain water.
After two months of treatment, and again after eight months, the scientists performed positron emission tomography (PET) scans to measure the levels of dopamine D2 receptors, a type of brain receptor important for experiencing reward and pleasure that has been linked to pleasure and drug abuse. After the eight-month treatment, animals were also tested for their propensity to self-administer cocaine.
Rats given the 2mg/kg dose of methylphenidate were significantly less likely to press a lever to self-administer cocaine, and received fewer self-initiated infusions of the drug following eight months of treatment than the lower-dose group or the control rats.
The changes observed in brain chemistry were specific to the age and duration of methylphenidate treatment: Specifically, after two months of treatment, brain scans revealed that both groups of treated rats had lower levels of dopamine D2 receptors in their brains than did control animals.
In contrast, after eight months of treatment, the brain scans revealed elevated levels of dopamine D2 receptors in treated rats compared with controls, with the higher-dose treatment group showing the highest level of D2 receptors. In the control group, D2 receptor levels declined with age.
Research at Brookhaven and elsewhere has suggested that low levels of dopamine D2 receptors may increase the likelihood of drug abuse, while elevated levels of dopamine D2 receptors may attenuate the propensity to abuse drugs.