A selective ALDH-2 inhibitor reduces anxiety in rats.
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 naïve 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-HT(2C) agonist, mCPP. CVT-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.
Overstreet
David H
DH
Bowles Center for Alcohol Studies, Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7178, United States. dhover@med.unc.edu
Knapp
Darin J
DJ
Breese
George R
GR
Diamond
Ivan
I
D000427:Alcohol Deterrents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors* / Q000502:physiology; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D014151:Anti-Anxiety Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D007529:Isoflavones / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D000427:Alcohol Deterrents; D014151:Anti-Anxiety Agents; C550386:CVT-10216; D007529:Isoflavones; D024101:Mitochondrial Proteins; C013908:daidzin; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C505112:Aldh2 protein, rat