Does ADHD Treatment Lead to Later Drug Abuse?

Chronic methylphenidate and amphetamine use among children and adolescents with ADHD could help pave the way for drug abuse in adulthood. According to a report published June 5 in the online Pharmacology, Biochemistry, and Behavior, the duration and timing of oral methylphenidate use may be key factors in determining the potential for drug abuse later in life.

“These findings indicate that methylphenidate effects in D2 receptor expression in striatum are sensitive not only to length of treatment but also to the developmental stage at which treatment is given,” Panayotis K. Thanos, PhD, neuroscientist at the Brookhaven National Laboratory in Upton, New York, and colleagues stated.

The investigators randomly assigned oral methylphenidate (1 or 2 mg/kg) or water to healthy periadolescent rats for eight months. At two months and eight months, the researchers measured D2 receptor availability, and after the end of the treatment period, the animals were tested on cocaine self-administration. Dr. Thanos and colleagues found significantly reduced rates of cocaine self-administration during adulthood in rats that were treated with 2 mg/kg methylphenidate for eight months, compared with rats receiving 1 mg/kg of treatment or rats receiving water. However, no significant differences were observed in rates of cocaine self-administration in rats treated with 1 mg/kg of methylphenidate versus control rats.

The availability of D2 dopamine receptors was significantly lower after two months of treatment in rats given either 1 or 2 mg/kg of methylphenidate compared with control rats, but after eight months of treatment it was significantly higher. In contrast, availability of D2 receptors in control rats decreased with age. Furthermore, rats given 2 mg/kg of methylphenidate showed greater D2 receptor–binding availability at eight months, compared to rats given 1 mg/kg of treatment and to control rats. The same was true for rats given 1 mg/kg of treatment, compared to control rats.

D2 RECEPTOR AVAILABILITY

The observed increase of D2 receptor expression at eight months could explain why cocaine self-administration was decreased in rats treated with methylphenidate. Prior studies have given “indirect evidence that the high D2 receptor availability in animals treated chronically with methylphenidate could underlie their attenuated administration of cocaine,” Dr. Thanos’ team pointed out. “Our data showing increases in D2 receptor availability at eight months of treatment would therefore suggest that chronic methylphenidate treatment (started in adolescence) attenuated cocaine self-administration during adulthood.”

However, the lower availability of D2 receptors at two months suggested that shorter treatment duration, or the age at which treatment effects are evaluated, could produce differing results. Decreased D2 receptor availability after two months of treatment might have made the rats more vulnerable to cocaine self-administration during early adulthood, but the researchers did not evaluate cocaine self-administration at two months.

The investigators noted that studies in humans have found decreases in D2 receptors in persons who abused drugs such as cocaine, while among participants who have not abused drugs, lower D2 receptor availability has been associated with reports of pleasurable response to IV methylphenidate. In addition, those with higher D2 receptor availability tended to report the treatment as unpleasant.                                                                 

—John Merriman

Suggested Reading
Thanos PK, Michaelides M, Benveniste H, et al. Effects of chronic oral methylphenidate on cocaine self-administration and striatal dopamine D2 receptors in rodents. Pharmacol Biochem Behav. 2007 June 5; [Epub ahead of print].

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