Dose effects of triazolam on brain activity during episodic memory encoding: a PET study.
BACKGROUND
Although it is well established that acute benzodiazepine administration impairs episodic memory encoding, little is known about the neuroanatomical substrates of this effect.


OBJECTIVE
The objective was to examine the acute dose effects of the benzodiazepine hypnotic triazolam on brain activity during episodic memory encoding.


METHODS
After oral capsule administration (placebo, 0.1, 0.2, and 0.4 mg/70 kg triazolam), regional cerebral blood flow (rCBF) was measured using positron emission tomography (PET) with 15O-H2O during performance of semantic categorization and orthographic categorization tasks in a double-blind, within-subject design in 12 healthy volunteers. The rCBF associated with episodic memory encoding was measured by subtracting the rCBF during orthographic categorization from that during semantic categorization and by examining correlations between brain activity during encoding and subsequent recognition memory performance.


RESULTS
Results in the placebo condition replicated those of nonpharmacological encoding studies, including activation in left ventrolateral prefrontal cortex. Correlations between brain activity and subsequent memory performance additionally showed medial temporal activation. Triazolam produced dose-related impairment in memory performance and dose-related deactivation in encoding-associated areas including right prefrontal cortex, left parahippocampal gyrus, and left anterior cingulate cortex.


CONCLUSIONS
Results are consistent with behavioral evidence that benzodiazepines impair prefrontal control processes as well as contextual memory and episodic binding processes thought to be controlled by the medial temporal lobe. In addition to elucidating the brain mechanisms underlying these benzodiazepine-induced behavioral deficits, results of this study also help validate hypotheses generated in nonpharmacological neuroimaging studies regarding the processes controlled by these brain regions.
Mintzer
Miriam Z
MZ
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA. mmintzer@jhmi.edu
Kuwabara
Hiroto
H
Alexander
Mohab
M
Brasic
James R
JR
Ye
Weiguo
W
Ernst
Monique
M
Griffiths
Roland R
RR
Wong
Dean F
DF
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D003071:Cognition / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D018757:GABA Modulators / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects*; D049268:Positron-Emission Tomography; D014229:Triazolam / Q000494:pharmacology*
D018757:GABA Modulators; D014229:Triazolam