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.
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