Alcohol
Volume 43, Issue 7 , Pages 531-539 , November 2009

Ethanol and acetaldehyde action on central dopamine systems: mechanisms, modulation, and relationship to stress

  • Miriam Melis

      Affiliations

    • “B.B. Brodie” Department of Neuroscience, University of Cagliari, Monserrato, Cagliari 09042, Italy
    • ,
  • Marco Diana

      Affiliations

    • “G. Minardi” Cognitive Neuroscience Laboratory, Department of Drug Science, University of Sassari, Via Muroni 23/A, Sassari 07100, Italy
    • ,
  • Paolo Enrico

      Affiliations

    • “G. Minardi” Cognitive Neuroscience Laboratory, Department of Drug Science, University of Sassari, Via Muroni 23/A, Sassari 07100, Italy
    • ,
  • Michela Marinelli

      Affiliations

    • Department of Cellular & Molecular Pharmacology, Rosalind Franklin University of Medicine and Science/Chicago Medical School, North Chicago, IL 60064, USA
    • ,
  • Mark S. Brodie

      Affiliations

    • Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL 60612-7342, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1-312-996-2373; fax: +1-312-996-1414.

Received 17 December 2008 ,Revised 3 May 2009 ,Accepted 15 May 2009.

References 

  1. Abi-Dargham A, Kegeles LS, Martinez D, Innis RB, Laruelle M. Dopamine mediation of positive reinforcing effects of amphetamine in stimulant naive healthy volunteers: results from a large cohort. Eur. Neuropsychopharmacol. 2003;13:459–468
  2. Alcaro A, Huber R, Panksepp J. Behavioral functions of the mesolimbic dopaminergic system: an affective neuroethological perspective. Brain Res. Rev. 2007;56:283–321
  3. Appel SB, Liu Z, McElvain MA, Brodie MS. Ethanol excitation of dopaminergic ventral tegmental area neurons is blocked by quinidine. J. Pharmacol. Exp. Ther. 2003;306:437–446
  4. Appel SB, Wise L, McDaid J, Koyama S, McElvain MA, Brodie MS. The effects of long chain length n-alcohols on the firing frequency of dopaminergic neurons of the ventral tegmental area. J. Pharmacol. Exp. Ther. 2006;318:1137–1145
  5. Arizzi-LaFrance MN, Correa M, Aragon CM, Salamone JD. Motor stimulant effects of ethanol injected into the substantia nigra pars reticulata: importance of catalase-mediated metabolism and the role of acetaldehyde. Neuropsychopharmacology. 2006;31:997–1008
  6. Bongiovanni M, See RE. A comparison of the effects of different operant training experiences and dietary restriction on the reinstatement of cocaine-seeking in rats. Pharmacol. Biochem. Behav. 2008;89:227–233
  7. Brodie MS. Increased ethanol excitation of dopaminergic neurons of the ventral tegmental area after chronic ethanol treatment. Alcohol Clin. Exp. Res. 2002;26:1024–1030
  8. Brodie MS, Appel SB. The effects of ethanol on dopaminergic neurons of the ventral tegmental area studied with intracellular recording in brain slices. Alcohol Clin. Exp. Res. 1998;22:236–244
  9. Brodie MS, Appel SB. Dopaminergic neurons in the ventral tegmental area of C57BL/6J and DBA/2J mice differ in sensitivity to ethanol excitation. Alcohol Clin. Exp. Res. 2000;24:1120–1124
  10. Brodie MS, Pesold C, Appel SB. Ethanol directly excites dopaminergic ventral tegmental area reward neurons. Alcohol Clin. Exp. Res. 1999;23:1848–1852
  11. Brodie MS, Shefner SA, Dunwiddie TV. Ethanol increases the firing of dopamine neurons of the ventral tegmental area in vitro. Brain Research. 1990;508:65–69
  12. Cabib S, Orsini C, Le Moal M, Piazza PV. Abolition and reversal of strain differences in behavioral responses to drugs of abuse after a brief experience. Science. 2000;289:463–465
  13. Camarini R, Hodge CW. Ethanol preexposure increases ethanol self-administration in C57BL/6J and DBA/2J mice. Pharmacol. Biochem. Behav. 2004;79:623–632
  14. Carroll ME. The role of food deprivation in the maintenance and reinstatement of cocaine-seeking behavior in rats. Drug Alcohol Depend. 1985;16:95–109
  15. Carroll ME, Meisch RA. Determinants of increased drug self-administration due to food deprivation. Psychopharmacology (Berl). 1981;74:197–200
  16. Chu B, Dopico AM, Lemos JR, Treistman SN. Ethanol potentiation of calcium-activated potassium channels reconstituted into planar lipid bilayers. Mol. Pharmacol. 1998;54:397–406
  17. Cools AR, Gingras MA. Nijmegen high and low responders to novelty: a new tool in the search after the neurobiology of drug abuse liability. Pharmacol. Biochem. Behav. 1998;60:151–159
  18. Dallman MF, Akana SF, Bhatnagar S, Bell ME, Choi S, Chu A, et al. Starvation: early signals, sensors, and sequelae. Endocrinology. 1999;140:4015–4023
  19. De Wit H, Uhlenhuth EH, Johanson CE. Individual differences in the reinforcing and subjective effects of amphetamine and diazepam. Drug Alcohol Depend. 1986;16:341–360
  20. Di Chiara G, Imperato A. Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic dopamine system of freely moving rats. Proc. Natl. Acad. Sci. U.S.A. 1988;85:5274–5278
  21. Diana M, Peana AT, Sirca D, Lintas A, Melis M, Enrico P. Crucial role of acetaldehyde in alcohol activation of the mesolimbic dopamine system. Ann. N.Y. Acad. Sci. 2008;1139:307–317
  22. Durstewitz D, Seamans JK, Sejnowski TJ. Dopamine-mediated stabilization of delay-period activity in a network model of prefrontal cortex. J. Neurophysiol. 2000;83:1733–1750
  23. Edenberg HJ. The genetics of alcohol metabolism: role of alcohol dehydrogenase and aldehyde dehydrogenase variants. Alcohol Res. Health. 2007;30:5–13
  24. Enrico P, Sirca D, Mereu M, Peana AT, Lintas A, Golosio A, et al. Acetaldehyde sequestering prevents ethanol-induced stimulation of mesolimbic dopamine transmission. Drug Alcohol Depend. 2009;100:265–271
  25. Foddai M, Dosia G, Spiga S, Diana M. Acetaldehyde increases dopaminergic neuronal activity in the VTA. Neuropsychopharmacology. 2004;29:530–536
  26. Font L, Aragon CM, Miquel M. Ethanol-induced conditioned place preference, but not aversion, is blocked by treatment with D-penicillamine, an inactivation agent for acetaldehyde. Psychopharmacology (Berl). 2006;184:56–64
  27. Font L, Aragon CM, Miquel M. Voluntary ethanol consumption decreases after the inactivation of central acetaldehyde by d-penicillamine. Behav. Brain Res. 2006;171:78–86
  28. Ford CP, Mark GP, Williams JT. Properties and opioid inhibition of mesolimbic dopamine neurons vary according to target location. J. Neurosci. 2006;26:2788–2797
  29. Genovese A, Dimaggio R, Lisanti MT, Piombino P, Moio L. Aroma composition of red wines by different extraction methods and Gas Chromatography-SIM/MASS spectrometry analysis. Ann. Chim. 2005;95:383–394
  30. Gessa GL, Muntoni F, Collu M, Vargiu L, Mereu G. Low doses of ethanol activate dopaminergic neurons in the ventral tegmental area. Brain Res. 1985;348:201–203
  31. Gonzalez-Burgos G, Kroner S, Krimer LS, Seamans JK, Urban NN, Henze DA, et al. Dopamine modulation of neuronal function in the monkey prefrontal cortex. Physiol. Behav. 2002;77:537–543
  32. Grimm JW, See RE. Cocaine self-administration in ovariectomized rats is predicted by response to novelty, attenuated by 17-beta estradiol, and associated with abnormal vaginal cytology. Physiol. Behav. 1997;61:755–761
  33. Hahn J, Tse TE, Levitan ES. Long-term K+ channel-mediated dampening of dopamine neuron excitability by the antipsychotic drug haloperidol. J. Neurosci. 2003;23:10859–10866
  34. Hansson L, Hedner T, Himmelmann A. Alcohol and hypertension—how are they linked?. Blood Press. 1999;8:3–4
  35. Hoover DJ, Brien JF. Acetaldehyde concentration in rat blood and brain during the calcium carbimide–ethanol interaction. Can. J. Physiol. Pharmacol. 1981;59:65–70
  36. Hopf FW, Martin M, Chen BT, Bowers MS, Mohamedi MM, Bonci A. Withdrawal from intermittent ethanol exposure increases probability of burst firing in VTA neurons in vitro. J. Neurophysiol. 2007;98:2297–2310
  37. Huber JD, Darling SF, Park KK, Soliman KF. The role of NMDA receptors in neonatal cocaine-induced neurotoxicity. Pharmacol. Biochem. Behav. 2001;69:451–459
  38. Hung HC, Lee EH. MPTP produces differential oxidative stress and antioxidative responses in the nigrostriatal and mesolimbic dopaminergic pathways. Free Radic. Biol. Med. 1998;24:76–84
  39. Ikemoto S, Wise RA. Mapping of chemical trigger zones for reward. Neuropharmacology. 2004;47(Suppl 1):190–201
  40. Imperato A, Di Chiara G. Preferential stimulation of dopamine release in the nucleus accumbens of freely moving rats by ethanol. J. Pharmacol. Exp. Ther. 1986;239:219–228
  41. Jamal M, Ameno K, Uekita I, Kumihashi M, Wang W, Ijiri I. Catalase mediates acetaldehyde formation in the striatum of free-moving rats. Neurotoxicology. 2007;28:1245–1248
  42. Khaliq ZM, Bean BP. Dynamic, nonlinear feedback regulation of slow pacemaking by A-type potassium current in ventral tegmental area neurons. J. Neurosci. 2008;28:10905–10917
  43. Koob GF. Alcoholism: allostasis and beyond. Alcohol Clin. Exp. Res. 2003;27:232–243
  44. Koyama S, Appel SB. A-type K+ current of dopamine and GABA neurons in the ventral tegmental area. J. Neurophysiol. 2006;96:544–554
  45. Koyama S, Brodie MS, Appel SB. Ethanol inhibition of m-current and ethanol-induced direct excitation of ventral tegmental area dopamine neurons. J. Neurophysiol. 2007;97:1977–1985
  46. Kreek MJ, Koob GF. Drug dependence: stress and dysregulation of brain reward pathways. Drug Alcohol Depend. 1998;51:23–47
  47. Lammel S, Hetzel A, Hackel O, Jones I, Liss B, Roeper J. Unique properties of mesoprefrontal neurons within a dual mesocorticolimbic dopamine system. Neuron. 2008;57:760–773
  48. Lapish CC, Seamans JK, Judson CL. Glutamate-dopamine cotransmission and reward processing in addiction. Alcohol Clin. Exp. Res. 2006;30:1451–1465
  49. Lewohl JM, Wilson WR, Mayfield RD, Brozowski SJ, Morrisett RA, Harris RA. G-protein-coupled inwardly rectifying potassium channels are targets of alcohol action. Nat. Neurosci. 1999;2:1084–1090
  50. Margolis EB, Lock H, Chefer VI, Shippenberg TS, Hjelmstad GO, Fields HL. Kappa opioids selectively control dopaminergic neurons projecting to the prefrontal cortex. Proc. Natl. Acad. Sci. U.S.A. 2006;103:2938–2942
  51. Margolis EB, Lock H, Hjelmstad GO, Fields HL. The ventral tegmental area revisited: is there an electrophysiological marker for dopaminergic neurons?. J. Physiol. 2006;577:907–924
  52. Margolis EB, Mitchell JM, Ishikawa J, Hjelmstad GO, Fields HL. Midbrain dopamine neurons: projection target determines action potential duration and dopamine D(2) receptor inhibition. J. Neurosci. 2008;28:8908–8913
  53. Marinelli M. The many facets of the locomotor response to a novel environment test: theoretical comment on Mitchell, Cunningham, and Mark (2005). Behav. Neurosci. 2005;119:1144–1151
  54. Marinelli M. Dopaminergic reward pathways and effects of stress. In:  al'Absi M editors. Stress and Addiction: Biological and Psychological Mechanisms. Amsterdam, The Netherlands: Elsevier Science; 2007;p. 41–83
  55. Marinelli M, Cooper DC, Baker LK, White FJ. Impulse activity of midbrain dopamine neurons modulates drug-seeking behavior. Psychopharmacology (Berl). 2003;168:84–98
  56. Marinelli M, Le Moal M, Piazza PV. Acute pharmacological blockade of corticosterone secretion reverses food restriction-induced sensitization of the locomotor response to cocaine. Brain Res. 1996;724:251–255
  57. Marinelli M, White FJ. Enhanced vulnerability to cocaine self-administration is associated with elevated impulse activity of midbrain dopamine neurons. J. Neurosci. 2000;20:8876–8885
  58. McCutcheon J, Marinelli M. Age matters. Eur. J. Neurosci. 2009;29:997–1014
  59. McDaid J, McElvain MA, Brodie MS. Ethanol effects on dopaminergic ventral tegmental area neurons during block of Ih: involvement of barium-sensitive potassium currents. J. Neurophysiol. 2008;100:1202–1210
  60. Melis M, Enrico P, Peana AT, Diana M. Acetaldehyde mediates alcohol activation of the mesolimbic dopamine system. Eur. J. Neurosci. 2007;26:2824–2833
  61. Melis M, Pillolla G, Perra S, Colombo G, Muntoni AL, Pistis M. Electrophysiological properties of dopamine neurons in the ventral tegmental area of Sardinian alcohol-preferring rats. Psychopharmacology (Berl). 2009;201:471–481
  62. Melis M, Spiga S, Diana M. The dopamine hypothesis of drug addiction: hypodopaminergic state. Int. Rev. Neurobiol. 2005;63:101–154
  63. Mereu G, Fadda F, Gessa GL. Ethanol stimulates the firing rate of nigral dopaminergic neurons in unanesthetized rats. Brain. Res. 1984;292:63–69
  64. Messing RO, Petersen PJ, Henrich CJ. Chronic ethanol exposure increases levels of protein kinase C delta and epsilon and protein kinase C-mediated phosphorylation in cultured neural cells. J. Biol. Chem. 1991;266:23428–23432
  65. Messing RO, Sneade AB, Savidge B. Protein kinase C participates in up-regulation of dihydropyridine-sensitive calcium channels by ethanol. J. Neurochem. 1990;55:1383–1389
  66. Mirenowicz J, Schultz W. Preferential activation of midbrain dopamine neurons by appetitive rather than aversive stimuli. Nature. 1996;379:449–451
  67. Moore SD, Madamba SG, Siggins GR. Ethanol diminishes a voltage-dependent K+ current, the M-current, in CA1 hippocampal pyramidal neurons in vitro. Brain Res. 1990;516:222–228
  68. Morzorati SL. VTA dopamine neuron activity distinguishes alcohol-preferring (P) rats from Wistar rats. Alcohol Clin. Exp. Res. 1998;22:854–857
  69. Morzorati SL, Marunde RL. Comparison of VTA dopamine neuron activity in lines of rats selectively bred to prefer or avoid alcohol. Alcohol Clin. Exp. Res. 2006;30:991–997
  70. Oades RD, Halliday GM. Ventral tegmental (A10) system: neurobiology. 1. Anatomy and connectivity. Brain Res. 1987;434:117–165
  71. Okamoto T, Harnett MT, Morikawa H. Hyperpolarization-activated cation current (Ih) is an ethanol target in midbrain dopamine neurons of mice. J. Neurophysiol. 2006;95:619–626
  72. Osborne JP, Mira DO, Pilone GJ, Liu SQ. Acetaldehyde metabolism by wine lactic acid bacteria. FEMS Microbiol. Lett. 2000;191:51–55
  73. Peana AT, Enrico P, Assaretti AR, Pulighe E, Muggironi G, Nieddu M, et al. Key role of ethanol-derived acetaldehyde in the motivational properties induced by intragastric ethanol: a conditioned place preference study in the rat. Alcohol Clin. Exp. Res. 2008;32:249–258
  74. Peinado RA, Moreno JA, Munoz D, Medina M, Moreno J. Gas chromatographic quantification of major volatile compounds and polyols in wine by direct injection. J. Agric. Food Chem. 2004;52:6389–6393
  75. Pfeffer AO, Samson HH. Oral ethanol reinforcement: interactive effects of amphetamine, pimozide and food-restriction. Alcohol Drug Res. 1985;6:37–48
  76. Pfeffer AO, Samson HH. Effect of pimozide on home cage ethanol drinking in the rat: dependence on drinking session length. Drug Alcohol Depend. 1986;17:47–55
  77. Pfeffer AO, Samson HH. Haloperidol and apomorphine effects on ethanol reinforcement in free feeding rats. Pharmacol. Biochem. Behav. 1988;29:343–350
  78. Piazza PV, Deminiere JM, Le Moal M, Simon H. Factors that predict individual vulnerability to amphetamine self-administration. Science. 1989;245:1511–1513
  79. Piazza PV, Le Moal M. The role of stress in drug self-administration. Trends Pharmacol. Sci. 1998;19:67–74
  80. Quertemont E, De Witte P. Conditioned stimulus preference after acetaldehyde but not ethanol injections. Pharmacol. Biochem. Behav. 2001;68:449–454
  81. Ramchandani VA, Bosron WF, Li TK. Research advances in ethanol metabolism. Pathol. Biol. (Paris). 2001;49:676–682
  82. Rodd ZA, Bell RL, McQueen VK, Davids MR, Hsu CC, Murphy JM, et al. Chronic ethanol drinking by alcohol-preferring rats increases the sensitivity of the posterior ventral tegmental area to the reinforcing effects of ethanol. Alcohol Clin. Exp. Res. 2005;29:358–366
  83. Rodd ZA, Bell RL, Melendez RI, Kuc KA, Lumeng L, Li TK, et al. Comparison of intracranial self-administration of ethanol within the posterior ventral tegmental area between alcohol-preferring and Wistar rats. Alcohol Clin. Exp. Res. 2004;28:1212–1219
  84. Rodd ZA, Bell RL, Zhang Y, Murphy JM, Goldstein A, Zaffaroni A, et al. Regional heterogeneity for the intracranial self-administration of ethanol and acetaldehyde within the ventral tegmental area of alcohol-preferring (P) rats: involvement of dopamine and serotonin. Neuropsychopharmacology. 2005;30:330–338
  85. Rodd ZA, Gryszowka VE, Toalston JE, Oster SM, Ji D, Bell RL, et al. The reinforcing actions of a serotonin-3 receptor agonist within the ventral tegmental area: evidence for subregional and genetic differences and involvement of dopamine neurons. J. Pharmacol. Exp. Ther. 2007;321:1003–1012
  86. Rodd ZA, Melendez RI, Bell RL, Kuc KA, Zhang Y, Murphy JM, et al. Intracranial self-administration of ethanol within the ventral tegmental area of male Wistar rats: evidence for involvement of dopamine neurons. J. Neurosci. 2004;24:1050–1057
  87. Rodd-Henricks ZA, Melendez RI, Zaffaroni A, Goldstein A, McBride WJ, Li TK. The reinforcing effects of acetaldehyde in the posterior ventral tegmental area of alcohol-preferring rats. Pharmacol. Biochem. Behav. 2002;72:55–64
  88. Rodefer JS, Carroll ME. Progressive ratio and behavioral economic evaluation of the reinforcing efficacy of orally delivered phencyclidine and ethanol in monkeys: effects of feeding conditions. Psychopharmacology (Berl). 1996;128:265–273
  89. Saito T, Lee JM, Tabakoff B. Ethanol's effects on cortical adenylate cyclase activity. J. Neurochem. 1985;44:1037–1044
  90. Samson HH, Cunningham CL, Czachowski CL, Chappell A, Legg B, Shannon E. Devaluation of ethanol reinforcement. Alcohol. 2004;32:203–212
  91. Serrano E, Pozo OJ, Beltran J, Hernandez F, Font L, Miquel M, et al. Liquid chromatography/tandem mass spectrometry determination of (4S,2RS)-2,5,5-trimethylthiazolidine-4-carboxylic acid, a stable adduct formed between D-(-)-penicillamine and acetaldehyde (main biological metabolite of ethanol), in plasma, liver and brain rat tissues. Rapid Commun. Mass Spectrom. 2007;21:1221–1229
  92. Shaham Y, Erb S, Stewart J. Stress-induced relapse to heroin and cocaine seeking in rats: a review. Brain Res. Brain Res. Rev. 2000;33:13–33
  93. Shalev U, Marinelli M, Baumann MH, Piazza PV, Shaham Y. The role of corticosterone in food deprivation-induced reinstatement of cocaine seeking in the rat. Psychopharmacology (Berl). 2003;168:170–176
  94. Sinha R. How does stress increase risk of drug abuse and relapse?. Psychopharmacology (Berl). 2001;158:343–359
  95. Solem M, McMahon T, Messing RO. Protein kinase A regulates regulates inhibition of N- and P/Q-type calcium channels by ethanol in PC12 cells. J. Pharmacol. Exp. Ther. 1997;282:1487–1495
  96. Stobbs SH, Ohran AJ, Lassen MB, Allison DW, Brown JE, Steffensen SC. Ethanol suppression of ventral tegmental area GABA neuron electrical transmission involves N-methyl-d-aspartate receptors. J. Pharmacol. Exp. Ther. 2004;311:282–289
  97. Vengeliene V, Siegmund S, Singer MV, Sinclair JD, Li TK, Spanagel R. A comparative study on alcohol-preferring rat lines: effects of deprivation and stress phases on voluntary alcohol intake. Alcohol Clin. Exp. Res. 2003;27:1048–1054
  98. Vetter CS, Doremus-Fitzwater TL, Spear LP. Time course of elevated ethanol intake in adolescent relative to adult rats under continuous, voluntary-access conditions. Alcohol Clin. Exp. Res. 2007;31:1159–1168
  99. Volkow ND, Fowler JS, Wang GJ, Swanson JM, Telang F. Dopamine in drug abuse and addiction: results of imaging studies and treatment implications. Arch. Neurol. 2007;64:1575–1579
  100. Volkow ND, Wang GJ, Franceschi D, Fowler JS, Thanos PP, Maynard L, et al. Low doses of alcohol substantially decrease glucose metabolism in the human brain. Neuroimage. 2006;29:295–301
  101. Wanat MJ, Hopf FW, Stuber GD, Phillips PE, Bonci A. Corticotropin-releasing factor increases mouse ventral tegmental area dopamine neuron firing through a protein kinase C-dependent enhancement of Ih. J. Physiol. 2008;586:2157–2170
  102. Wanat MJ, Sparta DR, Hopf FW, Bowers MS, Melis M, Bonci A. Strain specific synaptic modifications on ventral tegmental area dopamine neurons after ethanol exposure. Biol. Psychiatry. 2009;65:646–653
  103. Wang X, Treistman SN, Lemos JR. Two types of high-threshold calcium currents inhibited by omega-conotoxin in nerve terminals of rat neurohypophysis. J. Physiol. (London). 1992;445:181–199
  104. Ward RJ, Colantuoni C, Dahchour A, Quertemont E, De Witte P. Acetaldehyde-induced changes in monoamine and amino acid extracellular microdialysate content of the nucleus accumbens. Neuropharmacology. 1997;36:225–232
  105. Wise RA. Ventral tegmental glutamate: a role in stress-, cue-, and cocaine-induced reinstatement of cocaine-seeking. Neuropharmacology. 2009;56(Suppl 1):174–176
  106. Yang F, Feng L, Zheng F, Johnson SW, Du J, Shen L, et al. GDNF acutely modulates excitability and A-type K(+) channels in midbrain dopaminergic neurons. Nat. Neurosci. 2001;4:1071–1078
  107. Yoshimura M, Tabakoff B. Ethanol's actions on cAMP-mediated signaling in cells transfected with type VII adenylyl cyclase. Alcohol Clin. Exp. Res. 1999;23:1457–1461
  108. Zakhari S. Overview: how is alcohol metabolized by the body?. Alcohol Res. Health. 2006;29:245–254

PII: S0741-8329(09)00106-2

doi: 10.1016/j.alcohol.2009.05.004

Alcohol
Volume 43, Issue 7 , Pages 531-539 , November 2009

Article Tools