Influences of ?-Endorphins in Ethanol Consumption Patterns and Aquisition of a Conditioned Taste Aversion Mediated by the Drug
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Abstract
Rewarding effects of ethanol may be mediated in part by endogenous opioids. Ethanol alters ?-endorphin synthesis and release. ?endorphin heterozygous (HT) and knockout (KO) mice consume higher levels of a low-concentrated alcohol solution and show heightened predisposition to self-administer ethanol in comparison with wild-type (WT) mice (Grisel et al., 1999). This study was conducted in order to: i) reanalyze and extend previous results in terms of ethanol consumption profiles of ?-endorphin deficient mice; and ii) analyze conditioned aversive learning mediated by ethanol postabsorptive effects as a function of genetic capabilities to synthesize ?-endorphin. In Experiment 1, mice were evaluated in terms of consumption of a low (7%) ethanol solution in a twobottle free choice paradigm. Ethanol concentration was then increased to 10 % and voluntary intake consumption was tested. WT mice displayed significantly higher consumption levels and ethanol-preference scores than did KO mice, independently from ethanol concentration. HT mice drank more ethanol than did KO mice. In Experiment 2, mice (KO, HT and WT) were tested in a conditioned taste aversion paradigm in which a sodium chloride (NaCl) solution was paired with a 2-g/kg ethanol dose. Only HT and KO displayed a conditioned aversion when using 2-g/kg ethanol as unconditioned stimulus. The present results indicate that total or partial deficiency of ?-endorphin synthesis reduces ethanol preference and consumption. Furthermore, this study indicates that the lack of ?-endorphin synthesis exacerbates ethanol’s aversive postabsorptive effects which can in turn modulate self-administration patterns of the drug.
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Abate, P., Caeiro, X., Vivas, L. M., & Molina, J. C. (2009). Influences of ?-Endorphins in Ethanol Consumption Patterns and Aquisition of a Conditioned Taste Aversion Mediated by the Drug. Argentinean Journal of Behavioral Sciences, 1(1), 25–35. https://doi.org/10.32348/1852.4206.v1.n1.5301
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References
Allen, S.A., & Grisel, J.E. (2005). Absence of ethanolinduced sensitization in ?-endorphin deficient mice. Alcoholism Clinical and Experimental Research, 29 (suppl), 145A #824.
Bachmanov, A. A., Reed, D. R., Li, X., Li, S., Beauchamp, G. K., & Tordoff, M. G. (2002). Voluntary ethanol consumption by mice: genome-wide analysis of quantitative trait loci and their interactions in a C57BL/6ByJ x 129P3/J F2 intercross. Genome Research 12, 1257-1268.
Bals-Kubik, R., Ableitner, A., Herz, A., & Shippenberg, T. S. (1993). Neuroanatomical sites mediating the motivational effects of opioids as mapped by the conditioned place preference paradigm in rats. Journal of Pharmacological and Experimental Therapies 264, 489-495.
Broadbent, J., Muccino, K. J., & Cunningham, C. L. (2002). Ethanol-induced conditioned taste aversion in 15 inbred mouse strains. Behavioral Neuroscience 116, 138-148.
Chester, J. A., Lumeng, L., Li, T. K., & Grahame, N. J. (2003). High- and low-alcohol-preferring mice show differences in conditioned taste aversion to alcohol. Alcoholism Clinical and Experimental Research 27, 12-18.
Cordoba, N. E., Molina, J. C., Basso, A. M., & Orsingher, O. A. (1990). Perinatal undernutrition reduced ethanol intake preference in adult recovered rats. Physiology and Behavior 47, 1111-1116.
Crabbe, J. C., Kosobud, A., & Young, E. R. (1983). Genetic selection for ethanol withdrawal severity: differences in replicate mouse lines. Life Sciences 33, 955-962.
Cunningham, C. L., Fidler, T. L., & Hill, K. (2000). Animal models of alcohol’s motivational effects. Alcohol Research and Health 24, 85–92.
Cunningham, C. L., Niehus, J. S., & Noble, D. (1994). Species difference in sensitivity to ethanol's hedonic effects. Alcohol 10, 97-102.
Elkins, R. L., Walters, P. A., & Orr, T. E. (1992). Continued development and unconditioned stimulus characterization of selectively bred lines of taste aversion prone and resistant rats. Alcoholism Clinical and Experimental Research 16, 928-934.
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. Journal of Pharmacology and Experimental Therapies 87, 84-292.
Froehlich, J. C., Harts, J., Lumeng, L., & Li, T. K. (1988). Differences in response to the aversive properties of ethanol in rats selectively bred for oral ethanol preference. Pharmacology Biochemistry and Behavior 31, 215-222.
Gabriel, K. I., & Cunningham, C. L. (2005). Effects of topiramate on ethanol and saccharin consumption and preferences in C57BL/6J mice. Alcoholism Clinical and Experimental Research 29, 75-80.
Gianoulakis, C. (2004). Endogenous opioids and addiction to alcohol and other drugs of abuse. Current Topics of Medicine and Chemistry 4, 39-50.
Gianoulakis, C. (2001). Influence of the endogenous opioid system on high alcohol consumption and genetic predisposition to alcoholism. Journal of Psychiatry and Neuroscience 26, 304-18.
Gianoulakis, C. (1993). Endogenous opioids and excessive alcohol consumption. Journal of Psychiatry and Neuroscience 18, 148-156.
Gianoulakis, C., Krishnan, B., & Thavundayil, J. (1996). Enhanced sensitivity of pituitary beta-endorphin to ethanol in subjects at high risk of alcoholism. Archives of Genetical Psychiatry 53, 555.
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 acumbens. Journal of Neuroscience 18, 10663-10671.
Grahame, N. J., Low, M. J., & Cunningham, C. L. (1998). Intravenous self-administration of ethanol in betaendorphin-deficient mice. Alcoholism Clinical and Experimental Research 22, 1093-1098.
Grahame, N. J., Chester, J. A., Rodd-Henricks, K., Li, T. K., & Lumeng, L. (2001). Alcohol place preference conditioning in high- and low-alcohol preferring selected lines of mice. Pharmacology Biochemistry and Behavior 68, 805-814.
Grahame, N. J., Mosemiller, A. K., Low, M. J., & Froehlich, J. C. (2000). Naltrexone and alcohol drinking in mice lacking beta-endorphin by site-directed mutagenesis. Pharmacology Biochemistry and Behavior 67, 759-766.
Grisel, J. E., Bartels, J. L., Allen, S. A., & Turgeon, V. L. (2008). Influence of beta-Endorphin on anxious behavior in mice: interaction with EtOH. Psychopharmacology (Berl) 200, 105-15.
Grisel, J. E., Mogil, J. S., Grahame, N. J., Rubinstein, M., Belknap, J. K., Crabbe, J. C., & Low, M. J. (1999). Ethanol oral self-administration is increased in mutant mice with decreased beta-endorphin expression. Brain Research 835, 62-67.
Grisel, J. E., Grahame, N. J., Mogil, J. S., Belknap, J. K., & Low, M. J. (1995). Decreased voluntary ethanol consumption in transgenic mice lacking ?-endorphin. Society of Neuroscience Abstract 21, 699.
Khachaturian, H., Lewis, M. E., Schafer, M. K., & Watson, S. J. (1985). Anatomy of the CNS opioid systems. Trends of Neurological Sciences 10, 111-119.
Kieffer, B. L., & Gavèriaux-Ruff, C. (2002). Exploring the opioid system by gene knockout. Progress in Neurobiology 66, 285-306.
Kohl, R. R., Katner, J. S., Chernet, E., & McBride, W. J. (1998). Ethanol and negative feedback regulation of mesolimbic dopamine release in rats. Psychopharmacology 139, 79-85.
Kovacs, K. M., Szakall, I., O'Brien, D., Wang, R., Vinod, K. Y, Saito, M., Simonin, F., Kieffer, B. L., & Vadasz, C. (2005). Decreased oral self-administration of alcohol in kappa-opioid receptor knock-out mice. Alcoholism Clinical and Experimental Research 29, 730-738.
Opsahl, M. L., McClenaghan, M., Springbett, A., Reid, S., Lathe, R., Colman, A., & Whitelaw, C. B. A. (2002). Multiple effects of genetic background on variegated transgene expression in mice. Genetics 160, 1107-1112.
Oswald, L. M., & Wand, G. S. (2004). Opioids and alcoholism. Physiology and Behavior 81, 339-358.
Quintanilla, M. E., Callejas, O., & Tampier, L. (2001). Differences in sensitivity to the aversive effects of ethanol in low-alcohol drinking (UChA) and highalcohol drinking (UChB) rats. Alcohol 23, 177-182.
Racz, I., Schürmann, B., Karpushova, A., Reuter, M., Cichon, S., Montag, C., Fürst, R., Schütz, C., Franke, P. E., Strohmaier, J., Wienker, T.F., Terenius, L., Osby, U., Gunnar, A., Maier, W., Bilkei-Gorzó, A., Nöthen, M., & Zimmer, A. (2008). The opioid peptides enkephalin and beta-endorphin in alcohol dependence. Biological Psychiatry 64, 989-997.
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., & Cunningham, C. L. (1998). Ethanolinduced conditioned taste aversion in BXD recombinant inbred mice. Alcoholism Clinical and Experimental Research 22, 1234-1244.
Risinger, F. O., Malott, D. H., Prather, L. K., Niehus, D. R., & Cunningham, C. L. (1994). Motivational properties of ethanol in mice selectively bred for ethanol-induced locomotor differences. Psychopharmacology (Berl) 116, 207-216.
Roberts, A. J., McDonald, J. S., Heyser, C. J., Kieffer, B. L., Mathes, H. W., Koob, G. F., & Gold, L. H. (2000). ?Opioid receptor knockout mice do not self-administer alcohol. Pharmacological and Experimental Therapies 293, 1002-1008.
Rubinstein, M., Japon, M. A. & Low, M. J. (1993). Introduction of a point mutation into the mouse genome by homologous recombination in embryonic stem cells using a replacement type vector with a selectable marker. Nucleic Acids Research 21, 2613-2617.
Rubinstein, M., Mogil, J. S., Japon, M., Chan, E. C., Allen, R. G. & Low, M. J. (1996). Absence of opioid stressinduced analgesia in mice lacking beta-endorphin by site-directed mutagenesis. Proceedings of the National Academy of Sciences 93, 3995-4000.
Spanagel, R., & Weiss, F. (1999). The dopamine hypothesis of reward: past and current status. Trends in Neurosciences 22, 521-527.
US Department of Health and Human Services (2000) 10 th Special Report to the U.S Congress on Alcohol and Health. National Institutes of Health, National Institute of Alcohol Abuse and Alcoholism, Bethesda, MA.
Bachmanov, A. A., Reed, D. R., Li, X., Li, S., Beauchamp, G. K., & Tordoff, M. G. (2002). Voluntary ethanol consumption by mice: genome-wide analysis of quantitative trait loci and their interactions in a C57BL/6ByJ x 129P3/J F2 intercross. Genome Research 12, 1257-1268.
Bals-Kubik, R., Ableitner, A., Herz, A., & Shippenberg, T. S. (1993). Neuroanatomical sites mediating the motivational effects of opioids as mapped by the conditioned place preference paradigm in rats. Journal of Pharmacological and Experimental Therapies 264, 489-495.
Broadbent, J., Muccino, K. J., & Cunningham, C. L. (2002). Ethanol-induced conditioned taste aversion in 15 inbred mouse strains. Behavioral Neuroscience 116, 138-148.
Chester, J. A., Lumeng, L., Li, T. K., & Grahame, N. J. (2003). High- and low-alcohol-preferring mice show differences in conditioned taste aversion to alcohol. Alcoholism Clinical and Experimental Research 27, 12-18.
Cordoba, N. E., Molina, J. C., Basso, A. M., & Orsingher, O. A. (1990). Perinatal undernutrition reduced ethanol intake preference in adult recovered rats. Physiology and Behavior 47, 1111-1116.
Crabbe, J. C., Kosobud, A., & Young, E. R. (1983). Genetic selection for ethanol withdrawal severity: differences in replicate mouse lines. Life Sciences 33, 955-962.
Cunningham, C. L., Fidler, T. L., & Hill, K. (2000). Animal models of alcohol’s motivational effects. Alcohol Research and Health 24, 85–92.
Cunningham, C. L., Niehus, J. S., & Noble, D. (1994). Species difference in sensitivity to ethanol's hedonic effects. Alcohol 10, 97-102.
Elkins, R. L., Walters, P. A., & Orr, T. E. (1992). Continued development and unconditioned stimulus characterization of selectively bred lines of taste aversion prone and resistant rats. Alcoholism Clinical and Experimental Research 16, 928-934.
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. Journal of Pharmacology and Experimental Therapies 87, 84-292.
Froehlich, J. C., Harts, J., Lumeng, L., & Li, T. K. (1988). Differences in response to the aversive properties of ethanol in rats selectively bred for oral ethanol preference. Pharmacology Biochemistry and Behavior 31, 215-222.
Gabriel, K. I., & Cunningham, C. L. (2005). Effects of topiramate on ethanol and saccharin consumption and preferences in C57BL/6J mice. Alcoholism Clinical and Experimental Research 29, 75-80.
Gianoulakis, C. (2004). Endogenous opioids and addiction to alcohol and other drugs of abuse. Current Topics of Medicine and Chemistry 4, 39-50.
Gianoulakis, C. (2001). Influence of the endogenous opioid system on high alcohol consumption and genetic predisposition to alcoholism. Journal of Psychiatry and Neuroscience 26, 304-18.
Gianoulakis, C. (1993). Endogenous opioids and excessive alcohol consumption. Journal of Psychiatry and Neuroscience 18, 148-156.
Gianoulakis, C., Krishnan, B., & Thavundayil, J. (1996). Enhanced sensitivity of pituitary beta-endorphin to ethanol in subjects at high risk of alcoholism. Archives of Genetical Psychiatry 53, 555.
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 acumbens. Journal of Neuroscience 18, 10663-10671.
Grahame, N. J., Low, M. J., & Cunningham, C. L. (1998). Intravenous self-administration of ethanol in betaendorphin-deficient mice. Alcoholism Clinical and Experimental Research 22, 1093-1098.
Grahame, N. J., Chester, J. A., Rodd-Henricks, K., Li, T. K., & Lumeng, L. (2001). Alcohol place preference conditioning in high- and low-alcohol preferring selected lines of mice. Pharmacology Biochemistry and Behavior 68, 805-814.
Grahame, N. J., Mosemiller, A. K., Low, M. J., & Froehlich, J. C. (2000). Naltrexone and alcohol drinking in mice lacking beta-endorphin by site-directed mutagenesis. Pharmacology Biochemistry and Behavior 67, 759-766.
Grisel, J. E., Bartels, J. L., Allen, S. A., & Turgeon, V. L. (2008). Influence of beta-Endorphin on anxious behavior in mice: interaction with EtOH. Psychopharmacology (Berl) 200, 105-15.
Grisel, J. E., Mogil, J. S., Grahame, N. J., Rubinstein, M., Belknap, J. K., Crabbe, J. C., & Low, M. J. (1999). Ethanol oral self-administration is increased in mutant mice with decreased beta-endorphin expression. Brain Research 835, 62-67.
Grisel, J. E., Grahame, N. J., Mogil, J. S., Belknap, J. K., & Low, M. J. (1995). Decreased voluntary ethanol consumption in transgenic mice lacking ?-endorphin. Society of Neuroscience Abstract 21, 699.
Khachaturian, H., Lewis, M. E., Schafer, M. K., & Watson, S. J. (1985). Anatomy of the CNS opioid systems. Trends of Neurological Sciences 10, 111-119.
Kieffer, B. L., & Gavèriaux-Ruff, C. (2002). Exploring the opioid system by gene knockout. Progress in Neurobiology 66, 285-306.
Kohl, R. R., Katner, J. S., Chernet, E., & McBride, W. J. (1998). Ethanol and negative feedback regulation of mesolimbic dopamine release in rats. Psychopharmacology 139, 79-85.
Kovacs, K. M., Szakall, I., O'Brien, D., Wang, R., Vinod, K. Y, Saito, M., Simonin, F., Kieffer, B. L., & Vadasz, C. (2005). Decreased oral self-administration of alcohol in kappa-opioid receptor knock-out mice. Alcoholism Clinical and Experimental Research 29, 730-738.
Opsahl, M. L., McClenaghan, M., Springbett, A., Reid, S., Lathe, R., Colman, A., & Whitelaw, C. B. A. (2002). Multiple effects of genetic background on variegated transgene expression in mice. Genetics 160, 1107-1112.
Oswald, L. M., & Wand, G. S. (2004). Opioids and alcoholism. Physiology and Behavior 81, 339-358.
Quintanilla, M. E., Callejas, O., & Tampier, L. (2001). Differences in sensitivity to the aversive effects of ethanol in low-alcohol drinking (UChA) and highalcohol drinking (UChB) rats. Alcohol 23, 177-182.
Racz, I., Schürmann, B., Karpushova, A., Reuter, M., Cichon, S., Montag, C., Fürst, R., Schütz, C., Franke, P. E., Strohmaier, J., Wienker, T.F., Terenius, L., Osby, U., Gunnar, A., Maier, W., Bilkei-Gorzó, A., Nöthen, M., & Zimmer, A. (2008). The opioid peptides enkephalin and beta-endorphin in alcohol dependence. Biological Psychiatry 64, 989-997.
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., & Cunningham, C. L. (1998). Ethanolinduced conditioned taste aversion in BXD recombinant inbred mice. Alcoholism Clinical and Experimental Research 22, 1234-1244.
Risinger, F. O., Malott, D. H., Prather, L. K., Niehus, D. R., & Cunningham, C. L. (1994). Motivational properties of ethanol in mice selectively bred for ethanol-induced locomotor differences. Psychopharmacology (Berl) 116, 207-216.
Roberts, A. J., McDonald, J. S., Heyser, C. J., Kieffer, B. L., Mathes, H. W., Koob, G. F., & Gold, L. H. (2000). ?Opioid receptor knockout mice do not self-administer alcohol. Pharmacological and Experimental Therapies 293, 1002-1008.
Rubinstein, M., Japon, M. A. & Low, M. J. (1993). Introduction of a point mutation into the mouse genome by homologous recombination in embryonic stem cells using a replacement type vector with a selectable marker. Nucleic Acids Research 21, 2613-2617.
Rubinstein, M., Mogil, J. S., Japon, M., Chan, E. C., Allen, R. G. & Low, M. J. (1996). Absence of opioid stressinduced analgesia in mice lacking beta-endorphin by site-directed mutagenesis. Proceedings of the National Academy of Sciences 93, 3995-4000.
Spanagel, R., & Weiss, F. (1999). The dopamine hypothesis of reward: past and current status. Trends in Neurosciences 22, 521-527.
US Department of Health and Human Services (2000) 10 th Special Report to the U.S Congress on Alcohol and Health. National Institutes of Health, National Institute of Alcohol Abuse and Alcoholism, Bethesda, MA.