Stimulant Actions in Rodents: Implications for Attention-Deficit/Hyperactivity Disorder Treatment and Potential Substance Abuse

Most evidence supports the continued use of stimulants as the best available pharmacotherapy for the treatment of children with attention-deficit/hyperactivity disorder (ADHD), but little is known about possible enduring behavioral and neuroadaptational consequences of long-term stimulant exposure. Although a variety of preclinical studies, particularly those using methylphenidate (MP), have attempted to address these issues, most of these studies have used procedures that might not adequately simulate clinical treatment conditions, and results have not been entirely consistent. In particular, the rationale for selection of MP doses that simulate clinical exposure has not been well defined. We suggest that the use of more appropriate treatment conditions, including doses that result in plasma drug levels comparable to therapeutic levels, will provide a more accurate model for adequately assessing the therapeutic mechanisms and potential long-term consequences of stimulant psychotherapy in the treatment of ADHD.