A triazolam/amphetamine dose-effect interaction study: dissociation of effects on memory versus arousal.
BACKGROUND
In addition to producing robust memory impairment, benzodiazepines also induce marked sedation. Thus, it is possible that the observed amnestic effects are secondary to more global sedative effects and do not reflect a specific primary benzodiazepine effect on memory mechanisms.


OBJECTIVE
The objective was to use the nonspecific stimulant d-amphetamine to dissociate the sedative and memory-impairing effects of the benzodiazepine triazolam.


METHODS
Single oral doses of placebo, triazolam alone (0.25, 0.50 mg/70 kg), d-amphetamine sulfate alone (20, 30 mg/70 kg), and triazolam (0.25, 0.50 mg/70 kg) and d-amphetamine sulfate (20, 30 mg/70 kg) conjointly (at all dose combinations) were administered to 18 healthy adult participants across nine sessions in a double-blind, staggered-dosing, crossover design. In addition to standard data analyses, analyses were also conducted on z-score standardized data, enabling effects to be directly compared across measures.


RESULTS
Relative to the sedative measures, the memory measures generally exhibited a pattern of less reversal of triazolam's effects by d-amphetamine. The memory measures ranged in degree of reversal such that the most reversal was observed for reaction time on the n-back working memory task, and the least reversal was observed for accuracy on the Sternberg working memory task, with most measures showing an overall pattern of partial reversal.


CONCLUSIONS
Benzodiazepines have specific effects on memory that are not merely a by-product of the drugs' sedative effects, and the degree to which sedative effects contribute to the amnestic effects varies as a function of the particular memory process being assessed.
Mintzer
Miriam Z
MZ
Department of Psychiatry and Behavioral Sciences, Behavioral Biology Research Center, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA. mmintzer@jhmi.edu
Griffiths
Roland R
RR
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001143:Arousal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D018592:Cross-Over Studies; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004336:Drug Antagonism; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects*; D008570:Memory, Short-Term / Q000187:drug effects; D011939:Mental Recall / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D014229:Triazolam / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
D000697:Central Nervous System Stimulants; D006993:Hypnotics and Sedatives; D014229:Triazolam; D003913:Dextroamphetamine