The Effects of the Non-Benzodiazepine Hypnotic U-85575 on the Local Cerebral Glucose Utilization of Various Rat Brain Regions Using 14C-2-Deoxyglucose
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Authors
Schneider, Catherine C.
Issue Date
1990
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Benzodiazepines are found to produce hypnotic effects in the rat
brain by binding to a supramolecular complex, the benzodiazepine
receptor (BZR). This results in a stimulation of the inhibitory
neurotransmitter, GABA. Recently, a new non-benzodiazepine agent,
U-85575, was discovered to produce similar EEG patterns to
benzodiazepines. The purpose of the following study was to measure
the local cerebral glucose utilization (LCGU) at various regions
throughout rat brains treated with U-85575 alone or with the BZR
antagonist, Flumazenil, in order to interpret the actions of the agent
in comparison to those of benzodiazepines. LCaU can be related to
metabolic rate via Sokoloffs equation (Sokoloff, 1984). Brain slicing
and autoradiography were also employed to determine which areas
were depressed by the drug. Results show that although U -85575 is
obviously a hypnotic and a BZR agonist that affects important
anxiolytic regions (limbic system) and depressant areas (cortex,
hypothalamus), data reveal significant differences between the
drugs. While the areas affected by U -85575 correlated closely to
those depressed by the benzodiazepine, Triazolam; the actions of
U-85575 were not associated specifically with either BZR subtype. In
addition, key areas such as the spinal cord and hippocampus were
not depressed by U -85575 but were by benzodiazepines. Flumazenil
acted unexpectedly by not only antagonizing U-85575, but actually
stimulating several areas on its own. Flumazenil also reversed
depression by 10 mg/kg U-85575 moreso than 1 mg/kg U-85575
Based on these unexpected results, it is likely that both U -8557 5 and
Flumazenil act on additional receptors besides BZR to produce their
effects.
Description
vii, 40 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.