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Ethanol Self‐Administration in Deprived Rats: Effects of Ro15‐4513 Alone, and in Combination with Flumazenil (Ro15‐1788)
Author(s) -
June Harry L.,
Colker Richard E.,
Domangue Kevin R.,
Perry Lauren E.,
Hicks Leslie H.,
June Pamela L.,
Lewis Michael J.
Publication year - 1992
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1992.tb00628.x
Subject(s) - flumazenil , benzodiazepine , inverse agonist , antagonist , agonist , medicine , endocrinology , pharmacology , chemistry , receptor
Previous work in our laboratory demonstrated that Ro15‐4513, a partial inverse benzodiazepine agonist, decreases self‐administration of ethanol (ETOH) in rats maintained on a two‐bottle regmine of a saccharin ethanol solution (ES) and water over a 35‐day consumption period. The present study extended the consumption period to 60 days and examined the effects of Ro15‐4513 (2.5 mg/kg), flumazenil (Ro15‐1788) (8.0 mg/kg), and Ro15‐4513 in combination with Ro15‐1788 on the time course of ETOH self‐administration. High initial intake of ES observed during the first 4 weeks declined significantly over subsequent weeks. Ro15‐4513 pretreatment, however, resulted in significant reduction of ES, while significantly preventing the “normal” reduction of consumption as was observed under control conditions. The antagonistic actions of Ro15‐4513 were blocked/attenuated by the benzodiazepine receptor antagonist, Ro15‐1788, independent of whether consumption of the ES was low or high. Both Ro15‐4513 and Ro15‐1788 affected water intake differentially compared with vehicle‐injected controls. The results suggest that GABA‐benzodiazepine mechanisms may be important in altering chronic ETOH drinking patterns depending upon experience with ETOH, tolerance, or learning.