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Psychopharmacology (Berl). 2009 May;203(4):819-29. doi: 10.1007/s00213-008-1431-1. Epub 2009 Jan 6.

A therapeutic dose of zolpidem reduces thalamic GABA in healthy volunteers: a proton MRS study at 4 T.

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1
Behavioral Psychopharmacology Research Laboratory, McLean Hospital/Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA. slicata@mclean.harvard.edu

Abstract

BACKGROUND:

Zolpidem is a nonbenzodiazepine sedative/hypnotic that acts at GABA(A) receptors to influence inhibitory neurotransmission throughout the central nervous system. A great deal is known about the behavioral effects of this drug in humans and laboratory animals, but little is known about zolpidem's specific effects on neurochemistry in vivo.

OBJECTIVES:

We evaluated how acute administration of zolpidem affected levels of GABA, glutamate, glutamine, and other brain metabolites.

MATERIALS AND METHODS:

Proton magnetic resonance spectroscopy ((1)H MRS) at 4 T was employed to measure the effects of zolpidem on brain chemistry in 19 healthy volunteers. Participants underwent scanning following acute oral administration of a therapeutic dose of zolpidem (10 mg) in a within-subject, single-blind, placebo-controlled, single-visit study. In addition to neurochemical measurements from single voxels within the anterior cingulate (ACC) and thalamus, a series of questionnaires were administered periodically throughout the experimental session to assess subjective mood states.

RESULTS:

Zolpidem reduced GABA levels in the thalamus, but not the ACC. There were no treatment effects with respect to other metabolite levels. Self-reported ratings of "dizzy," "nauseous," "confused," and "bad effects" were increased relative to placebo, as were ratings on the sedation/intoxication (PCAG) and psychotomimetic/dysphoria (LSD) scales of the Addiction Research Center Inventory. Moreover, there was a significant correlation between the decrease in GABA and "dizzy."

CONCLUSIONS:

Zolpidem engendered primarily dysphoric-like effects and the correlation between reduced thalamic GABA and "dizzy" may be a function of zolpidem's interaction with alpha1GABA(A) receptors in the cerebellum, projecting through the vestibular system to the thalamus.

PMID:
19125238
PMCID:
PMC2818041
DOI:
10.1007/s00213-008-1431-1
[Indexed for MEDLINE]
Free PMC Article
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