Bases bioquímicas y neurobiológicas de la adicción al alcohol

F. Javier Ayesta

Resumen


Los últimos avances neurocientíficos han permitido profundizar en la fisiopatología del alcoholismo a nivel bioquímico y celular. Actualmente se sabe que los efectos agudos del etanol están fundamentalmente mediados por su interacción con neurotransmisores aminoácidos (primordialmente en los receptores GABAA y NMDA), así como cambios paralelos en determinadas aminas como la dopamina y la noradrenalina. Las respuestas neuroadpatativas en los receptores de aminoácidos subyacen probablemente en componentes importantes del síndrome de abstinencia, contribuyendo a la muerte neuronal que se encuentra en el alcoholismo crónico. Aunque no están tan bien comprendidas, las propiedades reforzadoras del etanol parecen estar mediadas fundamentalmente por la activación de receptores GABAA, la liberación de péptidos opioides, la interacción con receptores nicotínicos y la liberación indirecta de dopamina.


Palabras clave


alcohol; receptor GABAA; receptor NMDA; tolerancia; síndrome de abstinencia; canales de calcio; reforzamiento; sistemas de recompensa

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Referencias


(1) **Diamond I, Gordon AS. Cellular and molecular neuroscience of alcoholism. Physiol Rev 1997; 77: 1-20.

(2) *Eckardt MJ, File SE, Gessa GL, Grant KA, Guerri C, Hoffman PL, Kalant H, Koob GF, Li TK, Tabakoff B. Effects of moderate alcohol consumption on the central nervous system. Alcohol Clin Exp Res 1998; 22: 998-1040.

(3) *Faingold CL, N´Gouemo P, Riaz A. Ethanol and neurotransmitter interactions: from molecular to integrative effects. Prog Neurobiol 1998; 55:509-535.

(4) Gordon AS, Mochly-Rosen D, Diamond I. Alcoholism: a possible G-protein disorder. Proteins 1992; 8: 191-216.

(5) Stubbs CD, Slatter SJ. Ethanol and protein kinase C. Alcohol Clin Exp Res 1999; 23: 1552-1660.

(6) *Nutt D. Alcohol and the brain: pharmacological insights for psychiatrists. Br J Psychiatry 1999; 175: 114-119.

(7) Tabakoff B, Hellevuo K, Hoffman PL. Alcohol. En Schuster CR, Kuhar MJ (eds) Pharmacological aspects of drug dependence: toward an integrated neurobehavioral approach. Springer-Verlag (Berlín), 1996, pp: 373-458.

(8) Franks NP, Lieb WR. Molecular and cellular mechanisms of general anesthesia. Nature 1994; 367: 607-614.

(9) Moring J, Shoemaker WJ. Alcohol-induced changes in neuronal membranes. En Kranzler HR (ed) The pharmacology of alcohol abuse.

Springer-Verlag (Berlin), 1995, pp: 11-53.

(10) Costa E. From GABAA receptors diversity emerges a unified vision of gabaergic inhibition. Annu Rev Pharmacol Toxicol 1998; 38:321-350.

(11) Mehta AK, Ticku MK. An update on GABAA receptors. Brain Res Rev 1999; 29: 196-217.

(12) Wadfford KA, Whiting PJ. Ethanol potentiation of GABAA receptors requires phosphorylation of the alternatively spliced variant of the

gamma-2 subunit. FEBS Lett 1992; 313: 113-117.

(13) *Wirkner K, Poelchen W, Koles L, Muhlberg K, Scheibler P, Allgaier C, Illes P. Ethanol-induced inhibition of NMDA receptor channels. Neurochem

Int 1999; 35: 153-162.

(14) Givens B, McMahon K. Ethanol suppresses the induction of long-term potentiation in vivo. Brain Res 1995; 688: 27-33.

(15) Little HJ. The contribution of electrophysiology to knowledge of the acute and chronic effects of ethanol. Pharmacol Ther 1999; 84: 333-353.

(16) *Bardo MT. Neuropharmacological mechanisms of drug reward: beyond dopamine in the nucleus accumbens. Crit Rev Neurobiol 1998;

: 37-67.

(17) Soderpalm B, Ericson M, Olausson P, Blomqvist O, Engel JA. Nicotinic mechanisms involved in the dopamine activating and reinforcing properties of ethanol. Behav Brain Res 2000; 113: 85-96.

(18) **Altman J, Everitt BJ, Glautier S, Markou A, Nutt D, Oretti R, Phillips GD, Robbins TW. The biological, social and clinical bases of drug addiction: commentary and debate. Psychopharmacology 1996; 125: 285-345.

(19) Camí J, Ayesta FJ. Farmacodependencias. En Flórez J, Armijo JA, Mediavilla A (eds) Farmacología humana, Masson (Barcelona), 1997, pp:

-591.

(20) Ayesta FJ. Tolerance and physical dependence: physiological manifestations of chronic exposure to opioids. En Almeida OFX, Shippenberg TS (eds) Neurobiology of opioids, Springer-Verlag (Berlin), 1991, pp: 387-405.

(21) *Suwaki H, Kalant H, Higuchi S, Crabbe JC, Ohkuma S, Katsura M, Yoshimura M, Stewart RC, Li TK, Weiss F. Recent research on alcohol

tolerance and dependence. Alcohol Clin Exp Res 2001; 25: 189S-196S.

(22) Wolfe SM, Victor M. The relationship of hypomagnesaemia and alkalosis to alcohol withdrawal symptoms. Ann NY Acad Sci 1969; 162:

-984.

(23) Pandey SC, Davis JM, Pandey GN. Neurochemical findings in alcoholism and drug addiction and psychiatric comorbidity. En Miller NS (ed) The principles and practice of addictions in psychiatry, WB Saunder Co. (Philadelphia), 1997, pp: 70-78.

(24) *Gardner EL. Brain reward mechanisms. En Lowinson JH, Ruiz P, Millman RB, Langrod JG (eds) Substance abuse: a comprehensive textbook, Williams & Wilkins (Baltimore), 1997, pp: 51-85.

(25) Ikemoto S, Panksepp J. The role of nucleus accumbens-dopamine in motivated behavior: a unifying interpretation with special reference to

reward-seeking. Brain Res Rev 1999; 31: 6-41.

(26) Self DW, Nestler EJ. Molecular mechanisms of drug reinforcement and addiction. Annu Rev Neurosci 1995; 18:463-495.

(27) **Koob GF, Roberts AJ, Schulteis G, Parsons LH, Heyser CJ, Hyytia P, Merlo-Pich E, Weiss F. Neurocircuitry targets in ethanol reward and dependence. Alcohol Clin Exp Res 1998; 22: 3-9.

(28) *Le AD, Kiianmaa K, Cunningham CL, Engel JA, Ericson M, Söderpalm B, Koob GF, Roberts AJ, Weiss F, Hyytia P, Janhunen S, Mikkola J,

Bäckström P, Ponomarev I, Crabbe JC. Neurobiological processes in alcohol addiction. Alcohol Clin Exp Res 2001; 25: 144S-151S.

(29) Li TK, Spanagel R, Colombo G, McBride WJ, Porrino LJ, Suzuki T, Rodd-Henricks ZA. Alcohol reinforcement and voluntary ethanol consumption. Alcohol Clin Exp Res 2001, 25: 117S-126S.

(30) Di Chiara G, Acquas E, Tanda G. Etanol as a neurochemical surrogate of conventional reinforcers: the dopamine-opioid link. Alcohol 1996; 13: 13-17.

(31) Ulm RR, Volpicelli JR, Volpicelli JA. Opiates and alcohol self-administration in animals. J Clin Psychiatry 1995; 56: 5-14.

(32) Roberts AJ, McDonald JS, Heyser CJ, Kieffer BL, Matthes HWD, Koob GF, Gold LH. μ-opioid receptor knockout mice do not self-administer

alcohol. J Pharmacol Exp Ther 2000; 293: 1002-1008.

(33) Samson HA, Hoffman PL. Involvement of CNS cathecolamines in alcohol self-administration, tolerance, and dependence: preclinical studies.

En Kranzler HR (ed) The pharmacology of alcohol abuse. Springer-Verlag (Berlin) 1995, pp:121-137.

(34) *Noble EP. Alcoholism and the dopaminergic system. Addic Biol 1996; 1: 333-348.

(35) Hodge CW, Samson HH, Chapelle AM. Alcohol self-administration: further examination of the role of dopamine receptors in the nucleus

accumbens. Alcohol Clin Exp Res 1997; 21:1083-1091.

(36) Netsby P, Vanderschuren LJMJ, De Vries TC, Hogenboom F, Wardeh G, Mulder AH, Schoffelmeer ANM. Ehtanol, like psychostimulants and

morphine, causes long-lasting hyperreactivity of dopamine and acetylcholine neurons of rat nucleus accumbens: possible role in behavioral

sensitization. Psychopharmacology 1997; 133:69-76.

(37) *Schuckit MA, Smith TL, Daeppen JB, Eng M, Li TK, Hesselbrock VM, Nurnberger JI, Bucholz KK. Clinical relevance of the distinction between

alcohol dependence with and without a physiological component. Am J Psychiatry 1998: 155: 733-740.

(38) Bloom FE. Summation of the 1975 International Narcotic Research Club Conference. En Goldstein A (ed) The opiate narcotics: neurochemical

mechanisms in analgesia and dependence, Pergamon Press (Tucson), 1975, pp:251-259.




DOI: https://doi.org/10.20882/adicciones.520

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