Methylxanthines reverse the adipsic and aphagic syndrome induced by bilateral 6-hydroxydopamine lesions of the nigrostriatal pathway in rats

This study investigated whether methylxanthines (caffeine and theophylline) would restore food and water intake in rats made aphagic and adipsic by bi lateral 6-hydroxydopamine lesions of, the nigrostriatal bundle, and these r esults were compared with the effects of d-amphetamine, the dopamine D-1 ag onist SKF 38393, and the D-2/3 agonist quinpirole. In a separate experiment , we investigated whether the selective D-1 antagonist, SCH 23390, or the s elective D-2 antagonist, sulpiride, would prevent the caffeine-induced rest oration of food and water intake in bilaterally 6-hydroxydopamine denervate d rats. The results showed that caffeine? theophylline, and quinpirole sign ificantly reversed the aphagia and adipsia observed in lesioned animals. SK F 38393 had no significant effects on water intake, while it significantly restored food intake at the highest dose used. In contrast, d-amphetamine h ad no significant effects on food or water intake. Results from the second experiment showed that sulpiride attenuated the caffeine-induced restoratio n of food and water intake in lesioned rats to a greater extent than did SC H 23390. These data suggest that methylxanthines may mediate their effects on food and water intake in bilateral 6-hydroxydopamine-lesioned rats throu gh an action at the dopaminergic system. (C) 2000 Elsevier Science Inc.