Animal Models for Screening Drugs to Decrease Alcohol Consumption
Improved methods for treating alcoholism are greatly needed, and the use of pharmacological agents holds great promise. Development was previously hindered by the lack of an accepted animal model. Great emphasis has been placed upon designated criteria for an animal model of alcoholism, but such face validity is unimportant for finding better treatments. What really is needed is predictive validity—the ability to predict which drugs will reduce alcohol drinking in alcoholics. The simple model of rats voluntarily selecting unflavored ethanol has been shown to possess good predictive validity (Sinclair, 1987) and is currently being used for screening drugs for potential usefulness in alcoholism treatment.
The next step should be development of special animal models for screening drugs that act on specific components of alcohol drinking: e.g., blocking the deprivation-induced increase in craving or the accompanying arousal, correcting underlying disorders promoting drinking in some individuals, suppressing stimuli triggering drinking (e.g., withdrawal sensations or stimuli arising from the first drink after abstinence), satisfying the alcohol craving or blocking tolerance to satiety signals from alcohol. Particularly promising are drugs that block alcohol reinforcement and thus could be used to extinguish the alcohol-drinking response.
There is increasing evidence that pharmacological agents alter alcohol drinking in laboratory animals and in humans, and that pharmacological suppression of alcohol intake represents a feasible approach for improved treatment of alcoholism (Sinclair, 1987). The search for drugs that are useful against alcoholism must eventually proceed to clinical trials. Before that, however, a method is needed for screening the vast multitude of possibly beneficial drugs. This screening, by necessity, requires a good animal model.
KeywordsToxicity Depression Attenuation Morphine Expense
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- Altshuler, H.L and T.S.Shippenberg. Tetrahydroisoquinoline and opioid substrates of alcohol actions. Beta-Carbolines and Tetrahydroisoquinolines, Progress in Clinical Biological Research, 90: 329–344, 1982.Google Scholar
- Cloninger, C.R. Clinical heterogeneity in families of alcoholics. In:Genetic Aspects of AlcoholismK. Kiianmaa, B. Tabakoff and T. Saito (eds.), Helsinki: The Finnish Foundation for Alcohol Studies, pp. 55–65, 1989.Google Scholar
- Fruend, G. Comparison of alcohol dependence, withdrawal and hangover in humans and animals. In:Animal ModelsinAlcohol ResearchK.Eriksson, J.D.Sinclair, K.Kiianmaa (eds.) London: Academic, pp. 293–308, 1980.Google Scholar
- Gill, K. J. A critical evaluation of the use of animal models in alcohol research: An examination of voluntary alcohol consumption in rodents. Doctor Thesis, Dept Psychology, Concordia University, 1989.Google Scholar
- Ho, A.K.S. Ethanol preference, withdrawal and toxicities: modification by pharmacological agents. In K. Eriksson, J.D.Sinclair, & K.Kiianmaa (Eds.) Animal Models in Alcohol Research, London: Academic Press, pp. 173 – 178, 1980.Google Scholar
- Hyytiä, P. and J. D. Sinclair. Demonstration of lever pressing for oral ethanol by rats with no prior training or ethanol experience.Alcohol 6161 – 164, 1989.Google Scholar
- Li, T.-K. Genetic and neurobiological substrates of alcohol-seeking behavior & alcoholism. Presented at the 20th Nordic Meeting on Biological Alcohol Research, Espoo, Finland, May 13- 15, 1990 (Second plenary abstract in proceedings).Google Scholar
- Kornet, M., C. Goosen and J.M.Van Ree. The effect of naltrexone on alcohol consumption after alcohol deprivation in rhesus monkeys. Presented at the 20th Nordic Meeting on Biological Alcohol Research, Espoo, Finland, May 13 – 15, 1990 (Abstract 20 in proceedings).Google Scholar
- Sinclair, J. D. The alcohol-deprivation effect in monkeys.PsychonomicScience 25: 21 – 22, 1971.Google Scholar
- Sinclair, J.D. Comparison of the factors which influence voluntary drinking in humans and animals. In:Animal ModelsinAlcohol ResearchK.Eriksson, J.D.Sinclair, K.Kiianmaa (eds.) London: Academic, pp. 119–137, 1980.Google Scholar
- Sinclair, J.D. Drugs to decrease alcohol drinking.Annals of Medicine In press, 1990.Google Scholar
- Sinclair, J.D., M.Rusi, M.M.Airaksinen, and H.L.Altshuler. Relating TIQ’s, opiates, and ethanol.Beta-Carbolines and Tetrahydroisoquinolines, ProgressinClinical Biological Research, 90: 365 – 376, 1982.Google Scholar
- Sinclair, J.D. and R.J.Senter. Increased preference for ethanol in rats following alcohol deprivation.Psychonomic Science8: 11 – 12, 1967.Google Scholar
- Voltaire, A. O.Beck, S. Borg and H. Stibler. Clinical and biochemical features of relapse in alcohol dependent patients during longterm abstinence. Presented at the 19th Annual Nordic Meeting on Biological Alcohol Research, Varberg, Sweden, April 9 – 12, 1989 (Abstract 20 in proceedings).Google Scholar