Interaction of tetrahydropapaveroline with inhibition of dopa-decarboxylase by Ro 4-4602 in brain: effects on alcohol drinking in the rat.
The effects of the 1-aromatic amino acid decarboxylase inhibitor, Ro 4-4602 (benserazide), was determined on alcohol drinking induced in the rat by tetrahydropapaveroline (THP) injected by the intracerebroventricular (ICV) route. After ICV guide cannulae were implanted stereotaxically in 19 Sprague-Dawley rats, an artificial CSF solution containing 5.0 ng/micrograms THP was infused twice daily for 3 days in a volume of 5.0 microliters. Following a standard self-selection procedure, concentrations of alcohol which ranged from 3-30% were presented to the rats. A single maximally preferred solution, which in these rats ranged from 9-12% alcohol, was then offered in the presence of water. After a 4-day pretest in which alcohol intakes had stabilized, either 50 or 100 micrograms Ro 4-4602 plus THP were infused ICV to the animal during a 3-day period. Both doses of Ro 4-4602 significantly antagonized the g amount and proportional intakes of alcohol, but the higher dose was nearly twice as potent as the lower. During the 4-day postdrug test period, alcohol drinking continued to be suppressed. When THP was infused ICV over a 3-day period following the injections of Ro 4-4602, the predrug alcohol intake was partially reinstated, suggesting that this TIQ, when delivered directly into the brain, partly reversed the potent central action of Ro 4-4602. These results show that interference with the functional activity of central catecholamine pathways in the rat, by means of the inhibition of dopamine synthesis, serves to modify markedly the mechanisms underlying alcohol drinking in this species.(ABSTRACT TRUNCATED AT 250 WORDS)
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; D001545:Benserazide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006834:Hydrazines / Q000494:pharmacology*; D007980:Levodopa / Q000378:metabolism; D008297:Male; D010208:Papaverine / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D013765:Tetrahydropapaveroline / Q000494:pharmacology*
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D006834:Hydrazines; D007980:Levodopa; D013765:Tetrahydropapaveroline; D001545:Benserazide; D010208:Papaverine