Alprazolam attenuates the behavioral effects of d-amphetamine in humans.
The results of preclinical behavioral pharmacology studies suggest that gamma-aminobutyric acidA (GABAA) receptor modulators attenuate the behavioral effects of commonly abused stimulants such as amphetamines and cocaine under a variety of behavioral arrangements including drug discrimination and self-administration. In the present experiment, 6 healthy humans learned to discriminate 15-mg oral D-amphetamine. After acquiring the discrimination (ie, . > or = 80% correct responding on 4 consecutive days), the effects of a range of doses of D-amphetamine (0, 2.5, 5, 10, and 15 mg), alone and following pretreatment with alprazolam (0 and 0.5 mg), a GABAA receptor modulator, were assessed. D-Amphetamine alone functioned as a discriminative stimulus and produced stimulant-like self-reported drug effects (eg, increased scores on a Stimulant-Sensitive Adjective-Rating Scale). These effects were generally a function of dose. Alprazolam alone did not occasion D-amphetamine-like discriminative stimulus effects, nor did it increase ratings of sedation or impair performance. Alprazolam pretreatment significantly attenuated the discriminative stimulus effects of D-amphetamine, and some of the self-reported drug effects. Future human laboratory experiments should compare the behavioral effects of D-amphetamine alone and following pretreatment with alprazolam using other behavioral arrangements such as drug self-administration. Future laboratory experiments with humans should also determine if benzodiazepines with lower abuse potential (eg, oxazepam) might also attenuate the behavioral effects of D-amphetamine.
Rush
Craig R
CR
Department of Behavioral Science, College of Medicine, University of Kentucky, Lexington, KY 40536-0086, USA. crush2@uky.edu
Stoops
William W
WW
Wagner
Frances P
FP
Hays
Lon R
LR
Glaser
Paul E A
PE
D000293:Adolescent; D000328:Adult; D000339:Affect / Q000187:drug effects* / Q000502:physiology; D000525:Alprazolam / Q000494:pharmacology*; D000704:Analysis of Variance; D019540:Area Under Curve; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004192:Discrimination, Psychological / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology
D003913:Dextroamphetamine; D000525:Alprazolam