Cyanamide given ICV or systemically to the rat alters subsequent alcohol drinking.
Cyanamide or disulfiram serves to suppress volitional intake of alcohol presumably because of the toxic build-up of acetaldehyde dehydrogenase (AIDH). However, the presence of acetaldehyde systemically favors the in vivo synthesis of addictive-like metabolites in the brain which in turn enhance alcohol drinking. The purpose of this investigation, therefore, was to determine whether cyanamide administered to the rat, which did not have access to alcohol during treatment, would nevertheless affect the subsequent preference for alcohol. In the first experiment, cannulae were implanted bilaterally above the cerebral ventricle of 33 adult male Sprague-Dawley rats so that an artificial CSF or a solution of cyanamide could be infused intracerebroventricularly (ICV). Following post-operative recovery, each rat was tested for its alcohol preference by offering it water and a solution of ethyl alcohol which was increased over 8 days from 3-20%. After a single test concentration of alcohol (range of 5-9%) was selected for each individual animal presented with water over a 5-day interval, cyanamide was infused in a volume of 2.5 microliters per side three times daily for 4 days in one of the following total doses: 0.03, 0.1, 0.3, 0.5 or 1.0 mg. A second five-day preference test was run, and 6 weeks following cyanamide infusions a final 3-20% alcohol preference screen was run over 8 days. The results showed that a long-term, dose-dependent increase or decrease in alcohol intake occurred in those rats reactive to the drug.(ABSTRACT TRUNCATED AT 250 WORDS)
Critcher
E C
EC
Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill 27514.
Myers
R D
RD
D000428:Alcohol Drinking / Q000187:drug effects*; D000437:Alcoholism / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects; D003484:Cyanamide / Q000008:administration & dosage / Q000494:pharmacology*; D003486:Cyanides / Q000494:pharmacology*; D006801:Humans; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D003486:Cyanides; D003484:Cyanamide; D000444:Aldehyde Dehydrogenase