Human response to repeated low-dose d-amphetamine: evidence for behavioral enhancement and tolerance.
Previously, we reported progressively greater behavioral responses to repeated d-amphetamine in human subjects that represented a potential model of behavioral sensitization. To extend this work, 59 healthy volunteers were randomly assigned to one of three protocols: (1) placebo administered on days 1, 3, and 5 (PPP); (2) placebo administered on days 1 and 3, and d-amphetamine (0.25 mg/kg) on day 5 (PPA); and (3) d-amphetamine administered on days 1, 3, and 5 (AAA). Comparisons were made among the three groups to determine whether repeated d-amphetamine produced an increased behavioral response. Subjective ratings of vigor and euphoria exhibited the greatest response following the third dose of the AAA group, as hypothesized. In contrast, drug liking was greatest following a single or first d-amphetamine dose. These effects were greater in women. Progressive changes in subjective responses following repeated d-amphetamine administration may occur in healthy human subjects, although this effect may be greater for women.
Strakowski
S M
SM
Bipolar and Psychotic Disorders Research Program, Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0559, USA. strakosm@email.uc.edu
Sax
K W
KW
Rosenberg
H L
HL
DelBello
M P
MP
Adler
C M
CM
D000293:Adolescent; D000328:Adult; D001519:Behavior / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D016208:Databases, Factual; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D004361:Drug Tolerance; D005059:Euphoria / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012727:Sex Characteristics
D000697:Central Nervous System Stimulants; D003913:Dextroamphetamine