title: Benzodiazepine receptors mediate regional blood flow changes in the living human brain.
abstract: We studied the effects of a high-affinity gamma-aminobutyric acid (GABA)-benzodiazepine-receptor agonist (lorazepam) and an antagonist (flumazenil) in humans, using H2(15)O positron-emission tomography. Administration of lorazepam to healthy volunteers caused time- and dose-dependent reductions in regional cerebral blood flow and self-reported alterations in behavioral/mood parameters. Flumazenil administration reversed these changes. These observations indicated that benzodiazepine-induced effects on regional cerebral blood flow and mood/behavior are mediated at some level through GABA-benzodiazepine receptors, although the specific mechanism remains unclear. The approach described here provides a method for quantifying GABA-benzodiazepine-receptor-mediated neurotransmission in the living human brain and may be useful for studying the role of these receptors in a variety of neuropsychiatric disorders.
authors.affiliation: Clinical Neuroscience Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: E
authors.initials: E
authors.lastname: Matthew
authors.forename: P
authors.initials: P
authors.lastname: Andreason
authors.forename: K
authors.initials: K
authors.lastname: Pettigrew
authors.forename: R E
authors.initials: RE
authors.lastname: Carson
authors.forename: P
authors.initials: P
authors.lastname: Herscovitch
authors.forename: R
authors.initials: R
authors.lastname: Cohen
authors.forename: C
authors.initials: C
authors.lastname: King
authors.forename: C E
authors.initials: CE
authors.lastname: Johanson
authors.forename: D J
authors.initials: DJ
authors.lastname: Greenblatt
authors.forename: S M
authors.initials: SM
authors.lastname: Paul
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects; D001921:Brain / Q000098:blood supply* / Q000000981:diagnostic imaging; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology*; D007839:Functional Laterality; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D006801:Humans; D007700:Kinetics; D008140:Lorazepam / Q000494:pharmacology*; D008297:Male; D009928:Organ Specificity; D010104:Oxygen Radioisotopes; D011963:Receptors, GABA-A / Q000502:physiology*; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D014055:Tomography, Emission-Computed
chemical_list: D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D010104:Oxygen Radioisotopes; D011963:Receptors, GABA-A; D005442:Flumazenil; D008140:Lorazepam