title: Depression of thalamic metabolism by lorazepam is associated with sleepiness.
abstract: Though it is well recognized that the pharmacological actions of benzodiazepines are mediated by facilitation of GABAergic neurotransmission, the consequences of these changes in regional brain function are not well understood. This study measured regional brain glucose metabolism using Positron Emission Tomography and 2-deoxy-2[18F]fluoro-D-glucose in normal controls (n = 21) investigated with and without lorazepam (30 micrograms/kg IV) and with flumazenil given after lorazepam (n = 9). Lorazepam markedly decreased metabolism in thalamus (23 +/- 8%) and occipital cortex (19 +/- 8%), and flumazenil partially reversed these changes. Changes in metabolic activity in thalamus were significantly correlated with lorazepam-induced sleepiness (r = .69, df 20, p < .0005) and there was a trend of an association between the reversal by flumazenil of lorazepam-induced change in thalamus and in sleepiness (r = .63, df 8, p = .07). Benzodiazepine-induced changes in thalamic activity may account for their sedative properties.
authors.affiliation: Brookhaven National Laboratory, Upton, New York, USA.
authors.forename: N D
authors.initials: ND
authors.lastname: Volkow
authors.forename: G J
authors.initials: GJ
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Hitzemann
authors.forename: J S
authors.initials: JS
authors.lastname: Fowler
authors.forename: N
authors.initials: N
authors.lastname: Pappas
authors.forename: P
authors.initials: P
authors.lastname: Lowrimore
authors.forename: G
authors.initials: G
authors.lastname: Burr
authors.forename: K
authors.initials: K
authors.lastname: Pascani
authors.forename: J
authors.initials: J
authors.lastname: Overall
authors.forename: A P
authors.initials: AP
authors.lastname: Wolf
mesh_terms: D000328:Adult; D003071:Cognition / Q000187:drug effects; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000378:metabolism; D003864:Depression, Chemical; D005442:Flumazenil / Q000494:pharmacology; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008140:Lorazepam / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009778:Occipital Lobe / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D012890:Sleep / Q000187:drug effects; D013788:Thalamus / Q000187:drug effects / Q000378:metabolism*; D014055:Tomography, Emission-Computed
chemical_list: D019788:Fluorodeoxyglucose F18; D005442:Flumazenil; D003847:Deoxyglucose; D005947:Glucose; D008140:Lorazepam