BENZODIAZEPINE RECEPTORS MEDIATE REGIONAL BLOOD-FLOW CHANGES IN THE LIVING HUMAN BRAIN

We studied the effects of a high-affinity gamma-aminobutyric acid (GAB A) -benzodiazepine-receptor agonist (lorazepam) and an antagonist (flu mazenil) in humans, using (H2O)-O-15 positron-emission tomography. Adm inistration of lorazepam to healthy volunteers caused time- and dose-d ependent reductions in regional cerebral blood flow and self-reported alterations in behavioral/mood parameters. Flumazenil administration r eversed these changes. These observations indicated that benzodiazepin e-induced effects on regional cerebral blood flow and mood/behavior ar e mediated at some level through GABA-benzodiazepine receptors, althou gh the specific mechanism remains unclear. The approach described here provides a method for quantifying GABA-benzodiazepine-receptor-mediat ed neurotransmission in the living human brain and mag be useful for s tudying the role of these receptors in a variety of neuropsychiatric d isorders.