Interaction of tetrahydropapaveroline with inhibition of dopa-decarboxylase by Ro 4-4602 in brain: effects on alcohol drinking in the rat. 1989

F J Miñano, and B A McMillen, and R D Myers
Department of Pharmacology, East Carolina University School of Medicine, Greenville, NC 27858.

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)

UI MeSH Term Description Entries
D007980 Levodopa The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. L-Dopa,3-Hydroxy-L-tyrosine,Dopaflex,Dopar,L-3,4-Dihydroxyphenylalanine,Larodopa,Levopa,3 Hydroxy L tyrosine,L 3,4 Dihydroxyphenylalanine,L Dopa
D008297 Male Males
D010208 Papaverine An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels. Cerespan,Papaverine Hydrochloride,Pavabid,Pavatym,Hydrochloride, Papaverine
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D001923 Brain Chemistry Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states. Chemistry, Brain,Brain Chemistries,Chemistries, Brain
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006834 Hydrazines Substituted derivatives of hydrazine (formula H2N-NH2). Hydrazide
D000428 Alcohol Drinking Behaviors associated with the ingesting of ALCOHOLIC BEVERAGES, including social drinking. Alcohol Consumption,Alcohol Intake,Drinking, Alcohol,Alcohol Drinking Habits,Alcohol Drinking Habit,Alcohol Intakes,Consumption, Alcohol,Drinking Habit, Alcohol,Habit, Alcohol Drinking,Habits, Alcohol Drinking,Intake, Alcohol
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001545 Benserazide An inhibitor of DOPA DECARBOXYLASE that does not enter the central nervous system. It is often given with LEVODOPA in the treatment of parkinsonism to prevent the conversion of levodopa to dopamine in the periphery, thereby increasing the amount that reaches the central nervous system and reducing the required dose. It has no antiparkinson actions when given alone. Serazide,Seryltrihydroxybenzylhydrazine,DL-Serine 2-((2,3,4-trihydroxyphenyl)methyl)hydrazide,Ro 4-4602,Seryltrihydroxy Benzylhydrazine,Benzylhydrazine, Seryltrihydroxy,Ro 4 4602,Ro 44602

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