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 bilateral 6-hydroxydopamine lesions of the nigrostriatal bundle, and these results were compared with the effects of d-amphetamine, the dopamine D(1) agonist 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 selective D(2) antagonist, sulpiride, would prevent the caffeine-induced restoration of food and water intake in bilaterally 6-hydroxydopamine denervated rats. The results showed that caffeine, theophylline, and quinpirole significantly reversed the aphagia and adipsia observed in lesioned animals. SKF 38393 had no significant effects on water intake, while it significantly restored food intake at the highest dose used. In contrast, d-amphetamine had no significant effects on food or water intake. Results from the second experiment showed that sulpiride attenuated the caffeine-induced restoration of food and water intake in lesioned rats to a greater extent than did SCH 23390. These data suggest that methylxanthines may mediate their effects on food and water intake in bilateral 6-hydroxydopamine-lesioned rats through an action at the dopaminergic system.
Casas
M
M
Laboratori de Neuropsicofarmacologia, Hospital de la Santa Creu i Sant Pau, Avgda. St. Antoni Ma Claret, 167, 08025 Barcelona, Spain.
Prat
G
G
Robledo
P
P
Barbanoj
M
M
Kulisevsky
J
J
Jané
F
F
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000503:physiopathology; D003913:Dextroamphetamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004326:Drinking / Q000187:drug effects* / Q000502:physiology; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D016627:Oxidopamine / Q000633:toxicity*; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects* / Q000503:physiopathology; D013469:Sulpiride / Q000494:pharmacology; D013577:Syndrome; D013806:Theophylline / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology*
D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D014970:Xanthines; D019257:Quinpirole; D002110:Caffeine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D013469:Sulpiride; D016627:Oxidopamine; D013806:Theophylline; D003913:Dextroamphetamine