Problemas Relacionados al Alcohol: Bases Neurobiológicas del consumo de alcohol y Modelos Animales desarrollados para el abordaje de estas problemáticas

Contenido principal del artículo

Samanta M. March
Roberto Sebastián Miranda Morales

Resumen

El presente trabajo se centra en los modelos animales desarrollados para el abordaje del uso, abuso y dependencia de alcohol. Estos modelos han permitido el abordaje de diversas aristas vinculadas con la ingesta de alcohol, desde las disposiciones genéticas hasta los efectos de la exposición a la droga durante el desarrollo. También han permitido la evaluación de la eficacia de tratamientos farmacológicos y de los fenómenos asociados con el abuso de la droga, como el deseo incontrolable (craving), tolerancia y recaída. El articulo comienza con una breve reseña de las bases neurobiológicas del reforzamiento etílico, principalmente el rol del sistema opiáceo. De allí se abordan diferentes modelos, se describen modelos centrados en las bases genéticas, luego se describen modelos vinculados al estudio de fenómenos específicos observados en personas con desórdenes relacionados al uso de alcohol y finalmente modelos que subrayan cómo las experiencias tempranas con la droga pueden predisponer a un consumo problemático etapas posteriores de la vida.

Detalles del artículo

Cómo citar
March, S. M., & Miranda Morales, R. S. (2009). Problemas Relacionados al Alcohol: Bases Neurobiológicas del consumo de alcohol y Modelos Animales desarrollados para el abordaje de estas problemáticas. Revista Argentina De Ciencias Del Comportamiento, 1(1), 36–50. https://doi.org/10.32348/1852.4206.v1.n1.5302
Sección
Revisiones
Biografía del autor/a

Samanta M. March, Instituto Ferreyra

Facultad de Psicología, Universidad Nacional de Córdoba, Córdoba, Argentina.

Roberto Sebastián Miranda Morales, Instituto Ferreyra

Facultad de Psicología, Universidad Nacional de Córdoba, Córdoba, Argentina.

Citas

Aase, J.M. (1994). Clinical recognition of FAS: difficulties of detection and diagnosis. Alcohol Health & Research World, 18, 5-9.

Abel, E.L. (1984). Fetal alcohol syndrome and fetal alcohol effects. New York: Plenum Press.

Alcohol Research & Health, (2000) Prenatal Exposure to alcohol. Alcohol Research and Health, 24, 32-41.

Alexander, G.E., Crutcher, M.D. & DeLong, M.R. (1990) Basal gangliathalamocortical circuits: parallel substrates for motor, oculomotor, ‘prefrontal’ and ‘limbic’ function. Progress in. Brain Research. 85, 119–146.

Altshuler, H.L., Phillips, P.E. & Feinhandler, D.A. (1980) Alterations of ethanol self–administration by naltrexone. Life Sciences, 26, 679 – 688.

American Psychiatric Association (1994). Diagnostic and statistical manual of mental disorders (4º ed.) Washington DC: Author.

Arnold, H.M., Robinson, S.R., Spear, N.E. & Smotherman, W.P. (1993). Conditioned opioid activity in the rat fetus. Behavioral Neuroscience.107, 963–9.

Baer, J.S., Barr, H.M., Bookstein, F.L., Sampson, P.D. & Streissguth, A.P. (1998). Prenatal alcohol exposure and family history of alcoholism in the etiology of adolescent alcohol problems. Journal of Studies on Alcohol, 59,533-543.

Baer, J.S., Sampson, P.D., Barr, H.M., Connor, P.D. & Streissguth, A.P. (2003). A 21-year longitudinal analysis of the effects of prenatal alcohol exposure on young adult drinking. Archives of General Psychiatry, 60, 377-85.

Becker, H.C.; Randall, C.L.; Salo, A.L.; Saulnier, J.L. & Weathersby, R.T. (1994) Animal Research. Charting the course for FAS. Alcohol Health & Research World, 18, 10-16.

Benjamin, D., Grant, E. & Pohorecky, A. (1993). Naltrexone reverses ethanol-induced dopamine release in the nucleus accumbens in awake freely moving rats. Brain Research, 621, 137-40.

Besançon, F. (1993). Time to alcohol dependence after abstinence and first drink. Addiction, 88, 1647-1650.

Bonthius, D.J. & West, J.R. (1988). Blood alcohol concentration and microencephaly: A dose-response study in the neonatal rat. Teratology, 37, 223-231.

Bowers, B.J. (2000). Applications of transgenic and knockout mice in alcohol research. Alcohol Research & Health, 24, 175-184.

Burish, T.G., Maistro, S.A., Cooper, A.M. & Sobell, M.B. (1981). Effects of voluntary short-term abstinence on subsequent drinking patterns of college students. Journal of Studies on Alcohol, 42, 1013-1017.

Chotro, M.G. & Arias, C. (2003). Prenatal exposure to ethanol increases ethanol consumption: A conditioned response? Alcohol, 30, 19-28.

Ciccocioppo, R., Angeletti, S. & Weiss, F. (2001). Longlasting resistance to extinction of response reinstatement induced by ethanol-related stimuli: role of genetic ethanol preference. Alcoholism: Clinical and Experimental Research.,10, 1414-9.

Cunningham, C.L., Fidler, T.L. & Hill, K.G. (2000). Animal models of alcohol motivational effects. Alcohol Research & Health, 24, 85-92.

Davies, M. (2003). The role of GABAA receptors in mediating the effects of alcohol in the central nervous system. Journal of Psychiatry & Neuroscience, 28, 263–274.

DiChiara, G. & Emperato, A. (1988). Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proceedings of the National Academy of Science fo the United States of America, 85, 5274-8.

Domínguez, H.D., Chotro, M.G. & Molina, J.C. (1993). Alcohol in the amniotic fluid prior to caesarean delivery: effects of subsequent exposure to alcohol odor upon alcohol responsiveness. Behavioral & Neural Biology, 60, 129-138.

Domínguez, H.D., López, M.F. & Molina, J.C. (1998). Neonatal responsiveness to alcohol odor and infant alcohol intake as a function of alcohol experience during late gestation. Alcohol, 16, 109-117.

Driscoll, C.D., Streissguth, A. & Riley, E.P. (1990). Prenatal alcohol exposure: Comparability of effects in humans and animal models. Neurotoxicology and Teratology, 12, 231-237.

Ellis, F.W. & Pick, J.R. (1980). An animal model of the fetal alcohol syndrome in beagles. Alcoholism: Clinical and Experimental Research,, 4, 123-34.

Faas, A.E., Spontón, E.D., Moya, P.R. & Molina, J.C. (2000). Differential responsiveness to alcohol odor in human neonates. Effects of maternal consumption during gestation. Alcohol, 22, 7-17.

Fleming, M., Mihic, S.J. & Harris, R.A. (2001). Chapter 18: Ethanol. In J.G. Hardman and L.E. Limbird (Eds.), Goodman & Gilman’s the pharmacological basis of therapeutics 10th edition (429–445). New York: McGraw-Hill.

Frank, J., Lindholm, S.& Raaschou, P. (1998). Modulation of volitional ethanol intake in the rat by central deltaopioid receptors. Alcoholism: Clinical and Experimental Research, 22, 1185–1189.

Froehlich, J.C., Badia-Elder, N.E., Zink, R.W., McCullough, D.E. & Portoghese, P.S. (1998) Contribution of the opioid system to alcohol aversion and alcohol drinking behavior. The Journal of Pharmacology and Experimental Therapeutics, 287, 284-292.

Froehlich, J.C., Zweifel, M., Harts, J., Lumberg, L. & Li, T.K. (1991) Importance of delta opioid receptors in maintaining high alcohol drinking. Psychopharmacology (Berl), 103, 463–467.

Gianoulakis, C. (1990). Characterization of the effects of acute ethanol administration on the release of betaendorphin peptides by the

at hypothalamus. European Journal of Pharmacology, 180: 21-29.

Gianoulakis, C. (1996). Implications of endogenous opioids and dopamine in alcoholism: Human and basic science studies. Alcohol & Alcoholism, 31, 33–42.

Gianoulakis, C. (2004). Endogenous opioids and addiction to alcohol and other drugs of abuse. Current Topics in Medicinal Chemistry, 4, 39-50.

Gonzales, R.A. & Weiss, F. (1998). Suppression of ethanolreinforced behavior by naltrexone is associated with attenuation of the ethanol-induced increase in dialysate dopamine levels in the nucleus accumbens. Journal of Neuroscience, 18, 10663-10671.

Goodlet, C.R. & Johnson, T.B. (1999). Temporal windows of vulnerability within the third trimester equivalent: Why “knowing when” matters. En J. H. Hannigan, L.P. Spear, N.E. Spear & C.R. Goodlett (Eds.) Alcohol and Alcoholism: Effects on Brain and Development.

Hillsdale, NJ: Erlbaum.

Groenewegen, H.J. & Uylings, H.B. (2000) The prefrontal cortex and the integration of sensory, limbic and autonomic information. Progress in. Brain Research, 126, 3–28.

Gruest, N., Richer, P. & Hars B. (2004). Emergence of longterm memory for conditioned aversion in the rat fetus. Developmental Psychobiology, 44, 189-98.

Heimer, L. (2003). A new anatomical framework for neuropsychiatric disorders and drug abuse. American Journal of Psychiatry, 160, 1726–1739.

Heimer, L., Alheid, G.F., de Olmos, J.S., Groenewegen, H.J., Haber, S.N., Harlan, R.E. & Zahm, D.S. (1997). The accumbens: beyond the core-shell dichotomy. The Journal of Neuropsychiatry and Clinical Neuroscience, 9, 354–381.

Herz, A. (1997). Endogenous opioid system and alcohol addiction. Psychopharmacology (Berl), 192, 99-111.

Heyman, G.M. (2000). An economic approach to animal models of alcoholism. Alcohol Research & Health, 24, 132-140.

Hill, K.G. & Kiefer, S.W. (1997). Naltrexone treatment increases the aversiveness of alcohol for outbred rats. Alcoholism: Clinical and Experimental Research, 21, 637–641.

Hölter, S.M., Henniger, M.S., Lipkowski, A.W. & Spanagel, R. (2000). Kappa-opioid receptors and relapse-like drinking in long-term ethanol experienced rats. Psychopharmacology, 153, 93–102.

Hölter, S.M., Engelman, M., Kirschke, C., Liebsch, G., Landgraf, R. & Spanagel, R. (1998). Long-term ethanol self administration with repeated ethanol deprivation episodes changes ethanol drinking pattern and increases anxiety-related behaviour during ethanol deprivation in rats. Behavioural Pharmacology, 9, 41-48.

Hunt, P.S., Kraebel, K.S., Rabine, H., Spear, L.P. & Spear, N.E. (1993). Enhanced ethanol intake in preweanling rats following exposure to ethanol in a nursing context. Developmental Psychobiology, 26, 133-153.

Hyman, S.E. (2005). Addiction: a disease of learning and memory. American Journal of Psychiatry, 162, 1414-1422.

Jones, K.L., Smith, D.W., Ulleland, C.N. & Streissguth, A.P. (1973). Pattern of malformation in offspring of chronic alcoholic mothers. Lancet, 1, 1267-1271.

Kakidani, H., Furutami, Y., Takahashi, H., Noda, M., Mozimoto, Y. & Hiroshi, T. (1982). Cloning and sequence analysis of cDNA for porcine bneoendorphin/dynorphin precursors. Nature, 298, 245-249.

Kalivas, P.W. & Nakamura, M. (1999). Neural systems for behavioral activation and reward. Current Opinion in Neurobiology, 9, 223–227.

Kalivas, P.W. & Volkow, N.D. (2005). The neural basis of addiction: a pathology of motivation and choice. American Journal of Psychiatry, 162, 1403-13.

Kelly, S.J., Day, N. & Streissguth, A. (2000). Effects of prenatal alcohol on social behavior in human and other species. Neurotoxicology and Teratology, 22, 143-149

Kelly, S.J., Goodlett, C.R., Hulsether, S.A. & West, J.R. (1988). Impaired spatial navigation in adult female but not adult male rats exposed to alcohol during the brain growth spurt. Behavioral Brain Research, 27, 247-257.

Kline, J., Shrout, P., Stein, Z., Susser, M. & Warburton, D. (1980). Drinking during pregnancy and spontaneous abortion. Lancet, ii, 176-180

Kohl, R.R., Katner, J.S., Chernet, E. & McBride, W.J. (1998). Ethanol and negative feedback regulation of mesolimbic dopamine release in rats. Psychopahrmacology, 139, 79-85.

Krishnan – Sarin, S., Portoghese, P.S., Li, T.K. & Froehlich, J.C. (1995). The delta opioid receptor antagonist naltriben selectively attenuates alcohol intake in rats bred for alcohol preference. Pharmacology, Biochemistry & Behavior, 52, 153-159.

Koob, G.F., Sanna, P.P & Bloom, F.E. (1998) Neuroscience of addiction. Neuron, 21, 467-476.

Lemoine y cols. (1968). Citado en Aase, JM (1994) Clinical recognition of FAS, difficulties of detection and diagnosis. Alcohol Research & Health, 18, 5-9.

Liu, X. & Weiss, F. (2002a). Reversal of ethanol seeking behavior by D1 and D2 antagonists in an animal model of relapse: Differences in antagonist potency in previously ethanol-dependent versus non dependent rats. Pharmacology and Experimental Therapy, 300, 882-9.

Liu, X. & Weiss, F. (2002b). Additive effect of stress and drug cues on reinstatement of ethanol seeking: exacerbation by history of dependence and role of concurrent activation of corticotrophin-releasing factor and opioid mechanisms. The Journal of Neuroscience, 22, 7858-7861.

Lorenzo, P. & Ladero, J.M. (1999). Drogodependencias: farmacología, patología, psicología y legislación. Madrid: Editorial Médica Panamericana.

Ludwing, A.M., Wikler, A. & Stark, L.H. (1974). The first drink: Psychobiological aspects of craving. Archives of General Psychiatry, 30, 539-547.

March, SM; Abate, P; Spear, NE & Molina, JC (in press). Fetal exposure to moderate ethanol doses: heightened operant responsiveness elicited by ethanol-related reinforcers. Alcoholism: Clinical and Experimental Research.

Markou, A., Weiss, F., Gold, L.H., Caine, S.B., Schulteis, G. & Koob, G.F. (1993). Animal models of drug craving. Psychopharmacology (Berlin), 112, 163-182.

Mennella, J.A., Jagnow, C.P. & Beauchamp, G.K. (2001). Prenatal and postnatal flavor learning by human infants. Pediatrics, 107, E88.

Mennella, J.A. (1997). The human infant’s suckling responses to the flavor of alcohol in mother’s milk. Alcoholism: Clinical and Experimental Research, 21, 581-585.

Molina, J.C, Domínguez, H.D., López, M.F., Pepino, M.Y. & Fass, A.E. (1999). The role of fetal and infantile experiencece with alcohol in later recognition and acceptance patterns of the drug. En J.H Hanningan, L.P. Spear, N.E. Spear, N.E. & C.R. Goodlett (Eds.) Alcohol: Effects on brain and development (p 199-228).Mahwah NJ: Erlbaum.

Mustaca, A.E., & Kamenetzky, G.V. (2006). Alcoholismo y ansiedad: modelos animales. Internacional Journal of Psychology and Psychological Therapy, 6, 343-364.

NIAAA –National Institute of Alcohol Abuse and Alcoholism- (1992). The genetics of Alcoholism. Alcohol Alerts Nº 18. Recuperado el 10 de diciembre de 2000 en http://pubs.niaaa.nih.gov/publications/aa18.htm

Olive, M.F., Koenig, H.N., Nannini, M.A. & Hodge, C.W. (2001). Stimulation of endorphin neurotransmission in the nucleus accumbens by ethanol, cocaine, and amphetamine. The Journal of Neuroscience: the official journal of the Society for Neuroscience, 21, RC184.

Pautassi, R.M., Godoy, J.C., Spear, N.E. & Molina, J.C. (2002). Early responsiveness to stimuli paired with different stages within the state of alcohol intoxication. Alcoholism: Clinical and Experimental Research, 26, 644-54.

Pepino, M.Y. & Mennella, J.A. (2004). Advice given to women in Argentina about breast-feeding and the use of alcohol. Revista Panamericana de Salud Publica, 16, 408-14.

Pepino, M.Y., Kraebel, K.S., López, M.F., Spear, N.E. & Molina, J.C. (1998). Behavioral detection of low concentrations of ethanol in the preweanling rat. Alcohol, 15, 337-353.

Pepino, M.Y., López, M.F., Spear, N.E. & Molina, J.C. (1999). Infant rats respond differentially to alcohol after nursing from an alcohol intoxicated dam. Alcohol, 18,189-201.

Pepino, M.Y., Spear, N.E. & Molina, J.C. (2001). Nursing experiences with an alcohol intoxicated dam counteracts appetitive conditioned responses towards alcohol. Alcoholism: Clinical and Experimental Research, 25, 18-24.

Philpot, R.M., Badanich, K.A. & Kirsten, C.L. (2003). Place Conditioning: Age-related changes in the rewarding and aversive effects of alcohol. Alcoholism: Clinical and Experimental Research, 27, 593-599.

Pierce, R.C. & Salivas, P.W. (1997). A circuitry model of the expression of behavioral sensitization to amphetaminelike psychostimulants. Brain Research.Brain Research Reviews, 25, 192–216.

Ponce, L.F., Pautassi, R.M., Spear, N.E. & Molina, J.C. (2004). Nursing from an ethanol-intoxicated dam induces short- and long-term disruptions in motor performance and enhances later self-administration of the drug. Alcoholism: Clinical and Experimental Research, 28, 1039-1050.

Pueta, M., Abate, P., Haymal, O.B., Spear, N.E. & Molina, J.C. (2008). Ethanol exposure during late gestation and nursing in the rat: effects upon maternal care, ethanol metabolism and infantile milk intake. Pharmacology, Biochemistry, and Behavior, 91, 21-31.

Pueta, M., Abate, P., Spear, N.E. & Molina, J.C. (2003). Interaction between pre-and early postnatal alcoholrelated memories: Impact upon alcohol acceptance patterns. Abstract publicado en Alcoholism: Clinical and Experimental Research 27, Abstract N° 941, pp.162 A.

Pueta, M., Abate, P., Spear, N.E. & Molina, J.C. (2005). Interactions Between Ethanol Experiences During Late Gestation and Nursing: Effects upon Infantile and Maternal Responsiveness to Ethanol. International Journal of Comparative Psychology, 18, 207-224.

Rasmussen, D.D., Bryant, C.A., Boldt, B.M., Colasurdo, E.A., Levin, N. & Wilkinson, C.W. (1998). Acute alcohol effects on opiomelanocortinergic regulation. Alcoholism: Clinical and Experimental Research, 22, 789-801.

Risinger, F.O. & Cunnigham, C.L. (1992). Ethanol produces rapid biphasic hedonic effects. Annals of the New York Academy of Sciences, 634, 506-08.

Rodd, Z.A., Bell, R.L., Sable, H.J.K., Murphy, J.M. & McBride, W.J. (2004). Recent advances in animal models of alcohol craving and relapse. Pharmacology, ,Biochemistry, and Behavior, 79, 439-450.

Samsom, H.H., Pfeffer, A.O. & Tolliver, G.A. (1988). Oral ethanol self administration in the rat: Models of alcohol seeking behavior. Alcoholism: Clinical and Experimental Research, 12, 591-598.

Smotherman, W.P. (1982). Odor aversion learning by the rat fetus. Physiology & Behavior, 29, 769-71.

Sokol, R.J., Miller, S. & Reed, G. (1980). Alcohol abuse during pregnancy: An epidemiological study. Alcoholism: Clinical and Experimental Research, 4, 135-145.

Spanagel, R. (2000). Recent Animal Models of Alcoholism. Alcohol Research and Human Health, 24, 124-131.

Spanagel, R. & Hölter, S.M. (1999). Long-term alcohol selfadministration with repeated alcohol deprivation phases: An animal model of alcoholism? Alcohol and Alcoholim, 34, 231-243.

Spanagel, R & Hölter, S.M. (2000). Pharmacological validation of an animal model of alcoholism. Journal of Neural Transmission, 107, 669-680.

Spanagel, R. & Weiss, F. (1999). The dopamine hypothesis of reward: Past and current status. Trends in Neurosciences,. 22, 521-527.

Spanagel, R., Hölter, S.M., Allingham, K., Landgraf, R. & Zieglgänsberger, W. (1996). Acamprosate and alcohol: Effects on alcohol intake following alcohol deprivation in the rat. European Journal of Pharmacology, 305, 39-49.

Stratton, K., Howe, C. & Battaglia, F. (1996). Fetal alcohol syndrome: Diagnosis, epidemiology, prevention and treatment. Washington, DC: National Academy Press.

Streissguth, A. (1997). Fetal Alcohol Syndrome: A guide for families and communities. Baltimore, MD: Paul O. Brookes Publishing Co. .

Subramanian, M.G. & Abel, E.L. (1988). Alcohol inhibits suckling–induced prolactin release and milk yield. Alcohol, 5, 95-98.

Subramanian, M.G. (1999). Alcohol inhibits sucklinginduced oxytocin release in the lactating rat. Alcohol, 19, 51-55.

Tabakoff, B. & Hoffman, P.L. (2000). Animal Models in Alcohol Research. Alcohol Research & Health, 24, 77-84.

Ulm, R.R. & Volpicelli, J.R. (1995). Opiates and alcohol self-administration in animals. The Journal of Clinical Psychiatry, 56 Suppl 7 , 5-14.

Vangeline, V., Siegmund, S., Singer, M.V., Sinclair, J.D., Li, T.K. & Spanagel, R. (2003). A comparative study on alcohol-preferring rat lines: effects of deprivation and stress phases on voluntary alcohol intake. Alcoholism: Clinical and Experimental Research, 7, 1018-1031.

West, J.R., Goodlet, C.R., Bonthius, D.J., Hamre, K.M. & Marcussen, B.L. (1990). Cell population depletion associated with fetal alcohol brain damage: Mechanisms of BAC-dependent cell loss. Alcoholism: Clinical and Experimental Research, 14, 813-818.

Winger, G., Hofmann, F.G., & Woods, J.H. (1992) A handbook on drug and alcohol abuse: The biomedical aspects. (3º ed.). New York: Oxford University Press.

Wise, R. & Rompre, P. (1989). Brain dopamine and reward. Annual Review of Psychology, 40, 191-225.

Wolffgramm, J. (1991). An ethopharmacological approach to the development of drug addiction. Neuroscience and Biobehavioral Reviews, 15, 515-519.

Wolffgramm, J. & Heyne, A. (1991). Social behavior, dominance, and social deprivation determine drug choice. Pharmacology, Biochemistry, and Behavior, 38, 389-399.

Zahm, D.S. (2000). An integrative neuroanatomical perspective on some subcortical substrates of adaptive responding with emphasis on the nucleus accumbens. Neuroscience and Biobehavioral Reviews, 24, 85–105.