Inhibition of brain dopa-decarboxylase by RO 4-4602 infused ICV blocks alcohol drinking induced in rats by cyanamide

摘要: Following the stereotaxic implantation of chronic cannulae for intracerebroventricular (ICV) infusion, rats were given an alcohol preference test to establish their preferred concentration in comparison with water. After was removed, 15 mg/kg cyanamide then injected subcutaneously 4 days order maximize volitional intake single solutions alcohol, which these animals ranged from 7 15%. The l-dopa-decarboxylase inhibitor benserazide (Ro 4-4602) twice daily doses 50–100 failed alter rats' consumption either terms g/kg or proportional values. However, when ICV concentrations 10 ng–2.0 μg per 5.0 μl volume, attenuated drinking significantly. This reduction occurred a dose-dependent manner both absolute and intakes alcohol. Pre-treatment 1.0 ICV, removed situation, did not abolish subsequent ingestion but its peripheral administration (50 mg/kg) enhanced drinking. These results suggest that interference metabolic pathway dopamine serotonin synthesis, possibly through mechanism reduced formation aldehyde adducts brain, markedly alters pattern voluntary rat. Alternatively, could act by central inhibition dehydrogenase, turn would concomitantly elevate levels acetaldehyde thereby reduce