Central action of an inhibitor of brain dopa-decarboxylase, NSD-1015, on cyanamide-induced alcohol drinking in rats.
A cannula for repeated intracerebroventricular (ICV) infusion was implanted stereotaxically in 16 male Sprague-Dawley rats. Subsequently, an alcohol preference test was given to each animal to establish its preferred concentration in the presence of water. After the alcohol solution was removed, 15 mg/kg cyanamide was injected subcutaneously for 4 days to maximize volitional intake of the single preferred solution of alcohol, which ranged from 7-15% in these animals. The L-aromatic amino acid decarboxylase inhibitor, NSD-1015 (3-hydroxybenzylhydrazine dihydrochloride) was then given ICV twice daily in a volume of 5.0 microliters in the following doses: 0.005, 0.01, 0.1 and 1.0 micrograms. NSD-1015 in all doses attenuated the g/kg alcohol intake of the rats; however, this decline was significant only at the lowest dose, which was pharmacologically specific, since neither food nor water intakes were altered by the treatment. Following the ICV infusions of NSD-1015, alcohol drinking returned essentially to postcyanamide levels. Further, during the interval of administration of NSD-1015, the cyanamide-induced decline in food consumption was reversed. These observations are in agreement with previous findings obtained under similar experimental conditions with the L-aromatic amino acid decarboxylase inhibitor, benserazide (Ro4-4602). They suggest that central decarboxylation or other effects of this drug on limbic system structures involved in the intake of alcohol could comprise a part of the mechanism underlying the induction of drinking. Further support is also provided for the involvement of brain dopamine and/or serotonin in the specific pattern of alcohol consumption in the rat.
Miñano
F J
FJ
Department of Pharmacology, East Carolina University School of Medicine, Greenville, NC 27858.
McMillen
B A
BA
Myers
R D
RD
D000428:Alcohol Drinking / Q000187:drug effects*; D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D003484:Cyanamide / Q000494:pharmacology*; D003486:Cyanides / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D006834:Hydrazines / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D003486:Cyanides; D006834:Hydrazines; D003484:Cyanamide; C004297:3-hydroxybenzylhydrazine