Send to:

Choose Destination
See comment in PubMed Commons below
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.

Author information

  • 1Behavioral Psychopharmacology Research Laboratory, McLean Hospital/Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA.



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.


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


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.


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."


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.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Springer Icon for PubMed Central
    Loading ...
    Write to the Help Desk