Enhanced response to repeated d-amphetamine challenge: evidence for behavioral sensitization in humans

Behavioral sensitization is the process whereby intermittent stimulant exposure produces a time-dependent, enduring, and progressively more robust behavioral response. This process serves as an important model of neural plasticity and has also been proposed as a model for a variety of psychiatric syndromes; however, there are no published controlled studies of behavioral sensitization in human subjects. The authors report results from a double-blind, placebo-controlled study of repeated d-amphetamine challenges in a sample of normal human volunteers. Eleven consecutively recruited normal volunteers participated in this 4-day protocol. Each subject received two daily doses of d-amphetamine (0.25 mg/kg) separated by 48 hours that alternated with two daily doses of matched placebo. Symptoms (activity/energy level, mood, rate, and amount of speech) and eye-blink rates were measured hourly for 5 hours following drug administration. All four measures demonstrated significantly enhanced increases following the second amphetamine dose as compared to the first amphetamine dose and both placebo conditions. These findings suggest that behavioral sensitization is measurable in human subjects.