A critical evaluation of tetrahydroisoquinoline induced ethanol preference in rats. 1980

C Duncan, and R A Deitrich

It has been reported that certain tetrahydroisoquinoline compounds, especially salsolinol and tetrahydropaveroline (THP) when infused into the lateral ventricle of rats' brains results in increased preference for alcohol solutions. The effect is reported to be long-term, in that animals do not return to baseline drinking even months later. The current report provides a replicatin of the original experiments and also an extension of the work to complete dose-response curves for salsolinol and THP. Generally we have confirmed that rats of the Sprague-Dawley and Long-Evans strains do increase their alcohol intake in response to infused THP or salsolinol and that the effect is long lasting, up to 10 months. Such animals consume less alcohol at concentrations above 20% than below, in contrast to the previous reports where drinking was maintained at high concentrations of alcohol. While the animals will select alcohol in the face of a saccharin choice, they will not drink alcohol adulterated with quinine. We have failed to observe signs of dependence or withdrawal by these techniques and suggest that the original reports of these signs may have been a result of cellular damage caused by the long-term infusions. Additionally we have carried out extensive dose-response experiments with both salsolinol and THP. Doses of THP of 104 nmoles/day were inhibitory to alcohol drinking. We conclude that these compounds do shift these animals preference for alcohol relatively permanently, but not to the point of gross intoxication nor into the highly aversive range of alcohol concentration. We cannot confirm the reports that salsolinol or THP produce withdrawal symptoms when infused.

UI MeSH Term Description Entries
D007546 Isoquinolines A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
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
D002408 Catheters, Indwelling Catheters designed to be left within an organ or passage for an extended period of time. Implantable Catheters,In-Dwelling Catheters,Catheter, In-Dwelling,Catheter, Indwelling,Catheters, In-Dwelling,In Dwelling Catheters,In-Dwelling Catheter,Indwelling Catheter,Indwelling Catheters
D002552 Cerebral Ventricles Four CSF-filled (see CEREBROSPINAL FLUID) cavities within the cerebral hemispheres (LATERAL VENTRICLES), in the midline (THIRD VENTRICLE) and within the PONS and MEDULLA OBLONGATA (FOURTH VENTRICLE). Foramen of Monro,Cerebral Ventricular System,Cerebral Ventricle,Cerebral Ventricular Systems,Monro Foramen,System, Cerebral Ventricular,Systems, Cerebral Ventricular,Ventricle, Cerebral,Ventricles, Cerebral,Ventricular System, Cerebral,Ventricular Systems, Cerebral
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
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
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
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
D000431 Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES. Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol

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