PROGRESSIVE BEHAVIORAL-RESPONSE TO REPEATED D-AMPHETAMINE CHALLENGE -FURTHER EVIDENCE FOR SENSITIZATION IN HUMANS

Background: Behavioural sensitization is the process whereby intermitt ent stimulant exposure produces a time-dependent, enduring, and progre ssive behavioral response. Although animal models of sensitization are well established the phenomenon has been relatively little studied ii i humans. In a previous study, we reported enhanced responses followin g a second as compared to a first amphetamine dose in eye-blink rate a nd ratings of increased motor activity/energy, increased speech, and e levated mood in normal human volunteers. This current study extends th ose findings in a new sample of normal volunteers. Methods: Eleven nor mal human volunteers were administered three single oral doses of d-am phetamine (0.25 mg/kg) at 48-hour intervals, alternating with matched placebo in a randomized double-blind trial. Hourly behavioral ratings included eye-blink I-cite, symptoms (elevated mood, increased speech, increased motor activity/energy energy), and subjective drug effects. Results: Eye-blink rate and increased motor activity/ energy ratings p rogressively increased following each challenge with the third ampheta mine close response significantly greater than all other conditions 4 hours postadministration. Similar although less pronounced, responses were observed for elevated mood and subjective drug effect, Conclusion s: These results provide further evidence for sensitization of some am phetamine-induced behaviors in human subjects. (C) 1998 Society of Bio logical Psychiatry.