期刊
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
卷 94, 期 2, 页码 255-261出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbb.2009.09.004
关键词
ALDH-2 inhibitor; Social interaction test; Fawn-Hooded rats; Anxiogenic behavior; Ethanol withdrawal; DMCM; mCPP; Restraint stress
资金
- NIAAA
- CV Therapeutics
CVT-10216 is a highly selective, reversible inhibitor of ALDH-2 that reduces excessive alcohol drinking. Anxiety plays a role in alcoholism. The present study asks whether CVT-10216 has anxiolytic properties, as reflected in social interaction behavior in four unrelated rodent models: endogenous anxiety-like behavior in naive Fawn-Hooded rats, repeated alcohol-withdrawal-induced anxiety, restraint stress-induced anxiety and drug-induced anxiety. CVT-10216 counteracted anxiety in all models except that produced by the 5-HT2C agonist, mCPP. CVF-10216 exhibited both acute and prophylactic inhibitions of repeated alcohol-withdrawal-induced anxiety. Importantly, anxiogenic behavior induced by the benzodiazepine receptor inverse agonist, DMCM, was counteracted dose-dependently by CVT-10216. Thus, a non-addictive selective inhibitor of ALDH-2 has both anxiolytic and antidipsotropic properties, which may be dependent, in part on the involvement of the GABA-benzodiazepine system. (C) 2009 Elsevier Inc. All rights reserved.
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