title: Zolpidem reduces the blood oxygen level-dependent signal during visual system stimulation.
abstract: Zolpidem is a short-acting imidazopyridine hypnotic that binds at the benzodiazepine binding site on specific GABA(A) receptors to enhance fast inhibitory neurotransmission. The behavioral and receptor pharmacology of zolpidem has been studied extensively, but little is known about its neuronal substrates in vivo. In the present within-subject, double-blind, and placebo-controlled study, blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) at 3 Tesla was used to assess the effects of zolpidem within the brain. Healthy participants (n=12) were scanned 60 min after acute oral administration of zolpidem (0, 5, 10, or 20mg), and changes in BOLD signal were measured in the visual cortex during presentation of a flashing checkerboard. Heart rate and oxygen saturation were monitored continuously throughout the session. Zolpidem (10 and 20mg) reduced the robust visual system activation produced by presentation of this stimulus, but had no effects on physiological activity during the fMRI scan. Zolpidem's modulation of the BOLD signal within the visual cortex is consistent with the abundant distribution of GABA(A) receptors localized in this region, as well as previous studies showing a relationship between increased GABA-mediated neuronal inhibition and a reduction in BOLD activation.
authors.affiliation: Behavioral Psychopharmacology Research Laboratory, McLean Hospital/Harvard Medical School, 115 Mill Street, Belmont MA 02478, USA. slicata@mclean.harvard.edu
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Licata
authors.forename: Steven B
authors.initials: SB
authors.lastname: Lowen
authors.forename: George H
authors.initials: GH
authors.lastname: Trksak
authors.forename: Robert R
authors.initials: RR
authors.lastname: Maclean
authors.forename: Scott E
authors.initials: SE
authors.lastname: Lukas
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology* / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D010100:Oxygen / Q000097:blood*; D010775:Photic Stimulation; D010919:Placebos; D011725:Pyridines / Q000494:pharmacology* / Q000627:therapeutic use; D011963:Receptors, GABA-A / Q000502:physiology; D014793:Visual Cortex / Q000187:drug effects*; D055815:Young Adult; D000077334:Zolpidem
chemical_list: D006993:Hypnotics and Sedatives; D010919:Placebos; D011725:Pyridines; D011963:Receptors, GABA-A; D000077334:Zolpidem; D010100:Oxygen