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Isoquinolines, beta-carbolines and alcohol drinking: Involvement of opioid and dopaminergic mechanisms

Experientia volume 45, pages 436–443 (1989)Cite this article

Summary

Two classes of amine-aldehyde adducts, the tetrahydroisoquinoline (TIQ) and beta-carboline (THBC) compounds, have been implicated in the mechanism in the brain underlying the addictive drinking of alcohol. One part of this review focuses on the large amount of evidence unequivocally demonstrating not only the corporeal synthesis of the TIQs and THBCs but their sequestration in brain tissue as well. Experimental studies published recently have revealed that exposure to alcohol enhances markedly the endogenous formation of condensation products. Apart from their multiple neuropharmacological actions, certain adducts when delivered directly into the brain of either the rat or monkey, to circumvent the brain's blood-barrier system, can evoke an intense and dose-dependent increase in the voluntary drinking of solutions of alcohol even in noxious concentrations. That the abnormal intake of alcohol is related functionally to opioid receptors in the brain is likely on the basis of several dinstinct lines of evidence which include: the attenuation of alcohol drinking by opioid receptor antagoists; binding of a TIQ to opiate receptors in the brain; and marked differences in enkephalin values in animals genetically predisposed to the ingestion of alcohol. Finally, it is proposed that the dopaminergic reward pathways which traverse the meso-limbic-forebrain systems of the brain more than likely constitute an integrative anatomical substrate for the adduct-opioid cascade of neuronal events which promote and sustain the aberrant drinking of alcohol.

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References

  1. Adachi, J., Mizoi, Y., Fukunaga, T., Kogame, M., Ninomiya, I., and Naito, T., Effect of acetaldehyde on urinary salsolinol in healthy man after alcohol intake. Alcohol3 (1986) 215–220.

    Article  PubMed  Google Scholar 

  2. Adachi, J., Mizoi, Y., Fukunaga, T., Ueno, Y., Imamichi, H., Ninomiya, I., and Naito, T., Individual difference in urinary excretion of salsolinol in alcoholic patients. Alcohol3 (1986) 371–375.

    Article  PubMed  Google Scholar 

  3. Airaksinen, M. M., Mahonen, M., Tuomisto, L., Peura, P., and Eriksson, C. J. P., Tetrahydro-β-carbolines: effect of alcohol intake in rats. Pharmac. Biochem. Behav.18 (1983) 525–529.

    Article  Google Scholar 

  4. Alari, L., Lewander, T., and Sjoquist, B., The effect of ethanol on the brain catecholamine systems in female mice, rats, and guinea pigs. Alc. clin. exp. Res.11 (1987) 144–149.

    Google Scholar 

  5. Altshuler, H. L., Phillips, P. E., and Feinhandler, D. A., Alteration of ethanol self-administration by naltrexone. Life Sci.26 (1980) 679–688.

    Article  PubMed  Google Scholar 

  6. Blum, K., and Topel, H., Opioid peptides and alcoholism: genetic difficiency and chemical management. Estratto da: New Trends funct. Neurol.1 (1986) 71–83.

    Google Scholar 

  7. Blum, K., Briggs, A. H., Trachtenberg, M. C., DeLallo, L., and Wallace, J. E., Enkephalinase inhibition: Regulation of ethanol intake in genetically predisposed mice. Alcohol4 (1987) 449–456.

    Article  PubMed  Google Scholar 

  8. Blum, K., Briggs, A. H., Elston, S. F. A., Hirst, M., Hamilton, M. G., and Verebey, K., A common denominator theory of alcohol and opiate dependence: review of similarities and differences, in: Alcohol Tolerance and Dependence, pp. 371–391. Eds J. Crabbe and R. Rigter. Elsevier/North-Holland Biomedical Press, 1980.

  9. Blum, K., Briggs, A. H., DeLallo, L., Elston, S. F. A., and Ochoa, R., Whole brain methionine-enkephalin of ethanol-avoiding and ethanol-preferring C57BL mice. Experientia38 (1982) 1469–1470.

    PubMed  Google Scholar 

  10. Borg, S., Kvande, H., Rydberg, U., Terenius, L., and Wahlstrom, A., Endorphin levels in human cerebrospinal fluid during alcohol intoxication and withdrawal. Psychopharmacology78 (1982) 101–103.

    Article  PubMed  Google Scholar 

  11. Brien, J. F., Andrews, P. J., Loomis, C. W., and Page, J. A., Gasliquid chromatographic determination of salsolinol in the striatum of rat brain during the calcium carbimide-ethanol interaction. Can. J. Physiol. Pharmac.61 (1983) 632–640.

    Google Scholar 

  12. Britton, D. R., Rivier, C., Shier, T., Bloom, F., and Valet, W., In vivo and in vitro effects of tetrahydroisoquinolines and other alkaloids on rat pituitary function. Biochem. Pharmac.31 (1982) 1205–1211.

    Article  Google Scholar 

  13. Brown, Z. W., Amit, A., and Smith, B., Examination of the role of tetrahydroisquinoline alkaloids in the mediation of ethanol consumption in rats. Adv. expl. Med. Biol.126 (1980) 103–120.

    Google Scholar 

  14. Buckholtz, N. S., Neurobiology of tetrahydro-β-carbolines. Life Sci.27 (1980) 893–903.

    Article  PubMed  Google Scholar 

  15. Cardinale, G. J., Donnerer, J., Finck, A. D., Kantrowitz, J. D., Oka, K., and Spector, S., Morphine and codeine are endogenous components of human cerebrospinal fluid. Life Sci.40 (1987) 301–306.

    Article  PubMed  Google Scholar 

  16. Cascio, C. S., and Kellar, K. J., Tetrahydro-β-carbolines: Affinities for tryptamine and serotonergic binding sites. Neuropharmacology12 (1982) 1219–1221.

    Article  Google Scholar 

  17. Cashaw, J. L., Geraghty, C. A., McLaughlin, B. R., and Davis, V. E., A method for determination of subpicomole concentrations of tetrahydropapaveroline in rat brain by high-performance liquid chromatography with electrochemical detection. Analyt. Biochem.162 (1987) 274–282.

    Article  PubMed  Google Scholar 

  18. Cashaw, J. L., Geraghty, C. A., McLaughlin, B. R., and Davis, V. E., Effect of acute ethanol administration on brain levels of tetrahydropapaveroline in L-dopa-treated rats. J. Neurosci. Res.18 (1987) 497–503.

    Article  PubMed  Google Scholar 

  19. Clow, A., Stolerman, I. P., Murray, R. M., and Sandler, M., Ethanol preference in rats: Increased consumption after intraventricular administration of tetrahydropapaveroline. Neuropharmacology22 (1983) 563–565.

    Article  PubMed  Google Scholar 

  20. Chow, A., Topham, A., Saunders, J. B., Murray, R., Sandler, M., The role of salsolinol in alcohol intake and withdrawal, in: Aldehyde Adducts in Alcoholism, pp. 101–113. Ed. M. A. Collins. Alan Liss, New York 1985.

    Google Scholar 

  21. Cohen, G., The synaptic properties of some tetrahydroisoquinoline alkaloids. Alc. clin. expl. Res.2 (1978) 121–125.

    Google Scholar 

  22. Cohen, G., and Collins, M., Alkaloids from catecholamines in adrenal tissue: Possible role of alcoholism. Science167 (1970) 1749–1751.

    PubMed  Google Scholar 

  23. Collins, D. M., and Myers, R. D., Buspirone attenuates volitional alcohol intake in the chronically drinking monkey. Alcohol4 (1987) 49–56.

    Article  PubMed  Google Scholar 

  24. Collins, M. A., A possible neurochemical mechanism for brain and nerve damage associated with chronic alcoholism. Trends pharmac. Sci.3 (1982) 373–375.

    Article  Google Scholar 

  25. Collins, M. A., ed., Aldehyde Adducts in Alcoholism. Alan Liss, New York 1985.

    Google Scholar 

  26. Collins, M. A., and Kahn, A. J., Attraction to ethanol solutions in mice: induction by a tetrahydroisoquinoline derivative of L-Dopa. Subs. Alc. Actions/Misuse3 (1982) 299–302.

    Google Scholar 

  27. Collins, M. A., Hannigan, J. J., Origitano, T., Moura, D., and Osswald, W., On the occurrence, assay and metabolism of simple tetrahydroisoquinolines in mamalian tissues, in: Beta-Carbolines and Tetrahydroisoquinolines, pp. 155–166. Eds F. Bloom, J. Barchas, M. Sandler and E. Usdin. Alan Liss, New York 1982.

    Google Scholar 

  28. Collins, M. A., Nijm, W. P., Borge, G. F., Teas, G., and Goldfarb, C., Dopamine-related tetrahydroisoquinolines: significant urinary excretion by alcoholics after alcohol consumption. Science206 (1979) 1184–1186.

    PubMed  Google Scholar 

  29. Critcher, E. C., and Myers, R. D., Evidence for the hippocampus as a site of action for tetrahydropapaveroline (THP)-or cyanamide-induced alcohol drinking. Alcohol1 (1984) 167.

    Article  Google Scholar 

  30. Critcher, E. C., and Myers, R. D., Cyanamide given ICV or systemically to the rat alters subsequent alcohol drinking. Alcohol4 (1987) 347–353.

    Article  PubMed  Google Scholar 

  31. Critcher, E. C., Lin, C. I., Patel, J., and Myers, R. D., Attenuation of alcohol drinking in tetrahydroisoquinoline-treated rats by morphine and naltrexone. Pharmac. Biochem. Behav.18 (1983) 225–229.

    Article  Google Scholar 

  32. Dar, M. S., and Wooles, W. R., The effect of acute ethanol on dopamine metabolism and other neurotransmitters in the hypothalamus and corpus striatum of mice. J. neural Transm.60 (1984) 283–294.

    Article  PubMed  Google Scholar 

  33. Davis, V. E., and Walsh, M. J., Alcohol, amines and alkaloids: a possible biochemical basis for alcohol addiction. Science167 (1970) 1005–1007.

    PubMed  Google Scholar 

  34. Duncan, C., and Deitrich, R. A., A critical evaluation of tetrahydroisoquinoline induced ethanol preference in rats. Pharmac. Biochem. Behav.13 (1980) 265–281.

    Article  Google Scholar 

  35. Fertel, R. H., Greenwald, J. E., Schwarz, R., Wong, L., and Bianchine, J., Opiate receptor binding and analgesic effects of the tetrahydroisoquinolines salsolinol and tetrahydropapaveroline. Res. Commun. chem. Path. Pharmac.27 (1980) 3–16.

    Google Scholar 

  36. Geller, I., and Purdy, R., Alteration of ethanol preference in rats; effect of β-carbolines, pp. 295–302, in: Alcohol Intoxication and Withdrawall II. Ed. M. M. Gross. Plenum Press, New York 1975.

    Google Scholar 

  37. Genazzani, A. R., Nappi, G., Facchinetti, F., Mazzella, G. L., Parini, D., Sinforiani, E., Petraglia, F., and Savoldi, F., Central deficiency of β-endorphin in alcohol addicts. J. clin. Endocr. Metab.55 (1982) 583–586.

    PubMed  Google Scholar 

  38. Gianoulakis, C., and Gupta, A., Inbred strains of mice with variable sensitivity to ethanol exhibit differences in the content and processing of β-endorphin. Life Sci.39 (1986) 2315–2325.

    Article  PubMed  Google Scholar 

  39. Hamilton, M. G., Blum, K., and Hirst, M., Identification of an isoquinoline alkaloid after chronic exposure to ethanol. Alc. clin. expl. Res.2 (1978) 133–137.

    Google Scholar 

  40. Hannigan, J. J., and Collins, M. A., Tetrahydroisoquinolines and the serotonergic system. Drug Alc. Depend.4 (1979) 235–237.

    Article  Google Scholar 

  41. Hellevuo, K., and Korpi, E. R., Failure of Ro-15-4513 to antagonize ethanol in rat lines selected for differential sensitivity to ethanol and in Wistar rats. Pharmac. Biochem. Behav.30 (1988) 183–188.

    Article  Google Scholar 

  42. Hirst, M., Evans, D. R., and Gowdey, C. W., Salsolinol in urine of social drinkers. Prog. clin. biol. Res.90 (1985) 85–100.

    Google Scholar 

  43. Hirst, M., Evans, D. R., and Gowdey, C. W., Salsolinol in urine following chocolate consumption by social drinkers. Alc. Drug Res.7 (1987) 493–501.

    Google Scholar 

  44. Hirst, M., Evans, D. R., Gowdey, C. W., and Adams, A., The influences of ethanol and other factors on the excretion of urinary salsolinol in social drinkers. Pharmac. Biochem. Behav.22 (1985) 993–1000.

    Article  Google Scholar 

  45. Hirst, M., Adams, M. A., Okamoto, S., Gowdey, C. W., Evans, D. R., and LeBarr, J. M., Tetrahydroisoquinolines after ethanol consumption, in: β-Carbolines and Tetrahydroisoquinolines, pp. 81–96. Eds F. Bloom, J. Barchas, M. Sandler and E. Usdin. Alan Liss, New York 1982.

    Google Scholar 

  46. Ho, A. K. S., and Rossi, N., Suppression of ethanol consumption by MET-enkephalin in rats. J. Pharm. Pharmac.34 (1982) 118–119.

    Google Scholar 

  47. Hoffman, I. S., and Cubeddu, L. X., Presynaptic effects of tetrahydropapaveroline on striatal dopaminergic neurons. J. Pharnac. expl. Ther.220 (1982) 16–22.

    Google Scholar 

  48. Huttunen, P., and Myers, R. D., Tetrahydro-β-carboline micro-injected into the hippocampus induces an anxiety-like state in the rat. Pharmac. Biochem. Behav.24 (1986) 1733–1738.

    Article  Google Scholar 

  49. Huttunen, P., and Myers, R. D., Anatomical localization in hippocampus of tetrahydro-β-carboline-induced alcohol drinking in the rat. Alcohol4 (1987) 181–187.

    Article  PubMed  Google Scholar 

  50. Imperato, A., and Di Chiara, G., Preferential stimulation of dopamine release in the nucleus accumbens of freely moving rats by ethanol. J. Pharmac. expl. Ther.239 (1986) 219–228.

    Google Scholar 

  51. Kiianmaa, K., Andersson, K., and Fuxe, K., On the role of ascending dopamine systems in the control of voluntary ethanol intake and ethanol intoxication. Pharmac. Biochem. Behav.10 (1979) 605–608.

    Google Scholar 

  52. Koda, L. Y., Koob, G. F., Shier, W. T., and Bloom, F. E., Tetrahydropapaveroline induces small granular vesicles in brain dopamine fibres. Nature276 (1978) 281–283.

    PubMed  Google Scholar 

  53. Korpi, E. R., Sinclair, G. F., and Malminen, O., Dopamine D2 receptor binding in striatal membranes of rat lines selected for differences in alcohol-related behaviours. Pharmac. Toxic.61 (1987) 94–97.

    Google Scholar 

  54. Levy, A. D., and Ellison, G., Amphetamine-induced enhancement of ethanol consumption: Role of central catecholamines. Psychopharmacology86 (1985) 233–236.

    Article  PubMed  Google Scholar 

  55. Liljequist, S., Changes in the sensitivity of dopamine receptors in the nucleus accumbens and in the striatum induced by chronic ethanol administration. Acta pharmac. tox.43 (1978) 19–28.

    Google Scholar 

  56. Lister, R. G., and Nutt, D. J., Is Ro-15-4513 a specific alcohol antagonist? Trends Neurosci.10 (1987) 223–225.

    Article  Google Scholar 

  57. Lucchi, L., Rius, R. A., Uzumaki, H., Govoni, S., and Trabucchi, M., Chronic ethanol changes opiate receptor function in rat striatum. Brain Res.293 (1984) 368–371.

    Article  PubMed  Google Scholar 

  58. Makowski, E., and Ordonez, L. A., Behavioral alterations induced by formaldehyde-derived tetrahydroisoquinolines. Pharmac. Biochem. Behav.14 (1981) 639–643.

    Article  Google Scholar 

  59. Matsubara, K., Akane, A., Maseda, C., Takahashi, S., and Fukui, Y., Salsolinol in the urine of nonalcoholic individuals after long-term moderate drinking. Alc. Drug Res.6 (1986) 281–288.

    Google Scholar 

  60. Matsubara, K., Fukushima, S., and Fukui, Y., A systematic regional study of brain salsolinol levels during and immediately following chronic ethanol ingestion in rats. Brain Res.413 (1987) 336–343.

    Article  PubMed  Google Scholar 

  61. Melchior, C., and Collins, M. A., The route and significance of endogenous synthesis of alkaloids in animals, in: CRC Critical Reviews in Toxicology, pp. 313–356. CRC Press, Boca Rotan, Fl. 1982.

    Google Scholar 

  62. Melchior, C. L., Mueller, A., and Deitrich, R. A., Half-lives of salsolinol and tetrahydropapaveroline hydrobromide following intracerebroventricular injection. Biochem. Pharmac.29 (1980) 657–658.

    Article  Google Scholar 

  63. Melchior, C. L., and Myers, R. D., Genetic differences in ethanol drinking of the rat following injection of 6-OHDA, 5,6-DHT or 5,8-DHT into the cerebral ventricles. Pharmac. Biochem. Behav.5 (1976) 63–72.

    Article  Google Scholar 

  64. Melchior, C. L., and Myers, R. D., Preference for alcohol evoked by tetrahydropapaveroline (THP) chronically infused in the cerebral ventricle of the rat. Pharmac. Biochem. Behav.7 (1977) 19–35.

    Article  Google Scholar 

  65. Melchior, C. L., and Myers, R. D., Alcohol drinking induced in the rat after chronic injections of tetrahydropapaveroline (THP), salsolinol or noreleagnine in the brain, in: Alcohol and Aldehyde Metabolizing Systems, vol. III, pp. 545–554. Eds R. G. Thurman, J. R. Williamson, B. Chanee,and R. H. Drott. Academic Press, New York 1977.

    Google Scholar 

  66. Melchior, C. L., Simpson, C. W., and Myers, R. D., Dopamine release within forebrain sites perfused with tetrahydroisoquinolines or tryptoline in the rat. Brain Res. Bull.3 (1978) 631–634.

    Article  PubMed  Google Scholar 

  67. Meller, E., Friedman, E., Schweitzer, J. W., and Friedhoff, A. J., Tetrahydro-β-carbolines: Specific inhibitors of Type A monoamine oxidase in rat brain. J. Neurochem.28 (1977) 995–1000.

    PubMed  Google Scholar 

  68. Messiha, F. S., Larson, J. W., and Geller, I., Voluntary ethanol drinking by the rat: Effects of 2-aminoethylisothiouronium salt, a modifier of NAD: NADH and noreleagnine, a β-carboline derivative. Pharmacology15 (1977) 400–406.

    PubMed  Google Scholar 

  69. Minano, F. J., and Myers, R. D., Inhibition of dopa-decarboxylase in brain by Ro4-4602 on voluntary intake of alcohol induced by cyanamide. Psychopharmacology, (1989) in press.

  70. Murphy, J. M., McBride, W. J., Gatto, G. J., Lumeng, L., and Li, T.-K., Effects of acute ethanol administration on monamine and metabolite content in forebrain regions of ethanol-tolerant and-non-tolerant alcohol-preferring (P) rats. Pharmac. Biochem. Behav.29 (1988) 169–174.

    Article  Google Scholar 

  71. Myers, R. D., Psychopharmacology of alcohol. A. Rev. Pharmac. Toxic.18 (1978) 125–144.

    Article  Google Scholar 

  72. Myers, R. D., Pharmacological effects of amine-aldehyde condensation products, in: Alcohol Tolerance and Dependence, pp. 339–370. Eds H. Rigter and J. Crabbe. Elsevier, The Netherlands 1980.

    Google Scholar 

  73. Myers, R. D., Multiple metabolite theory, alcohol drinking and the alcogene, in: Aldehyde Adducts in Alcoholism, pp. 201–220. Ed. M. A. Collins. Alan Liss, New York 1985.

    Google Scholar 

  74. Myers, R. D., Alkaloid metabolites and addictive drinking of alcohol. NIAAA Research Monograph 17, pp. 268–284. Eds N. C. Chang and H. M. Chao. 1985.

  75. Myers, R. D., and Critcher, E. C., Naloxone alters alcohol drinking induced in the rat by tetrahydropapaveroline (THP) infused ICV. Pharmac. Biochem. Behav.16 (1982) 827–836.

    Article  Google Scholar 

  76. Myers, R. D., and Melchior, C. L., Alcohol drining in the rat after destruction of serotonergic and catecholaminergic neurons in the brain. Res. Commun. chem. Path. Pharm.10 (1975) 363–378.

    PubMed  Google Scholar 

  77. Myers, R. D., and Melchior, C. L., Alcohol drinking: Abnormal intake caused by tetrahydropapaveroline in brain. Science196 (1977) 554–556.

    PubMed  Google Scholar 

  78. Myers, R. D., and Melchior, C. L., Differential actions on voluntary alcohol intake of tetrahydroisoquinolines or a β-carboline infused chronically in the ventricle of the rat. Pharmac. Biochem. Behav.7 (1977) 381–392.

    Article  Google Scholar 

  79. Myers, R. D., and Oblinger, M., Alcohol drinking in the rat induced by acute intracerebral infusion of two tetrahydroisoquinolines and a β-carboline. Drug Alc. Depend.2 (1977) 469–483.

    Article  Google Scholar 

  80. Myers, R. D., and Privette, T. H., A neuroanatomical substrate for alcohol drinking: Identification of tetrahydropapaveroline (THP)-reactive sites in the rat brain. Brain Res. Bull.22 (1989) in press.

  81. Myers, R. D., and Ruwe, W. D., Is alcohol-induced poikilothermia mediated by 5-HT and catecholamine receptors or by ionic set-point mechanism in the brain? Pharmac. Biochem. Behav.16 (1982) 321–327.

    Article  Google Scholar 

  82. Myers, R. D., Borg, S., and Mossberg, R., Antagonism by naltrexone of voluntary alcohol selection in the chronically drinking macaque monkey. Alcohol3 (1986) 383–388.

    Article  PubMed  Google Scholar 

  83. Myers, R. D., Garrison, J. L., and Critcher, E. C., Degradation characteristics of two tetrahydroisoquinolines at room and body temperature: HPLC determination with electrochemical detection. J. liquid Chromat.6 (1983) 343–352.

    Google Scholar 

  84. Myers, R. D., McCaleb, M. L., and Ruwe, W. D., Alcohol drinking induced in the monkey by tetrahydropapaveroline (THP) infused into the cerebral ventricle. Pharmac. Biochem. Behav.16 (1982) 995–1000.

    Article  Google Scholar 

  85. Myers, R. D., Melchior, C., and Swartzwelder, H. S., Amine-aldehyde metabolites and alcoholism: Fact, myth or uncertainy. Subs. Alc. Actions/Misuse1 (1980) 223–238.

    Google Scholar 

  86. Myers, R. D., Swartzwelder, H. S., and Holahan, W., Effect of hippocampal lesions produced by intracerebroventricular kainic acid on alcohol drinking in the rat. Brain Res. Bull.10 (1983) 333–338.

    Article  PubMed  Google Scholar 

  87. Myers, W. D., Ng, K. T., Marzuki, S., Myers, R. D., and Singer, G., Alteration of alcohol drinking in the rat by peripherally self-administered acetaldehyde. Alcohol1 (1984) 229–236.

    Article  PubMed  Google Scholar 

  88. Myers, W. D., Ng, K. T., Singer, G., Smythe, G. A., and Duncan, M. W., Dopamine and salsolinol levels in rat hypothalami and striatum after schedule-induced self-injection (SISI) of ethanol and acetaldehyde. Brain Res.358 (1985) 122–128.

    Article  PubMed  Google Scholar 

  89. Myers, W. D., Mackenzie, L., Ng, K. T., Singer, G., Smythe, G. A., and Duncan, M. W., Salsolinol and dopamine in rat medial basal hypothalamus after chronic ethanol exposure. Life Sci.36 (1985) 309–314.

    Article  PubMed  Google Scholar 

  90. Nesterick, C. A., and Rahwan, R. G., Detection of endogenous salsolinol in neonatal rat tissue by a radioenzymatic-thin layer chromatographic assay. J. Chromat.164 (1979) 205–216.

    Google Scholar 

  91. Nimit, Y., Schulze, I., Cashaw, J. L., Ruchirawat, S., and Davis, V. E., Interaction of catecholamine-derived alkaloids with central neurotransmitter receptors. J. Neurosci. Res.10 (1983) 175–189.

    Article  PubMed  Google Scholar 

  92. Nimitkitpaisan, Y., and Skolnick, P., Catecholamine receptors and cyclic AMP formation in the central nervous system: effects of tetrahydroisoquinoline derivatives. Life Sci.23 (1978) 373–382.

    Article  Google Scholar 

  93. O'Neill, P. J., and Rahwan, R. G., Absence of formation of brain salsolinol in ethanol-dependent mice. J. Pharmac. expl. Ther.200 (1977) 306–313.

    Google Scholar 

  94. Origitano, T. C., and Collins, M. A., Confirmation of an unexpected brain O-methylation pattern for the dopamine-derived tetrahydroisoquinoline, salsolinol. Life Sci.26 (1980) 2061–2065.

    Article  PubMed  Google Scholar 

  95. Perry, T. L., Jones, K., and Hansen, S., Tetrahydroisoquinoline lacks dopaminergic nigrostriatal neurotoxicity in mice. Neurosci. Lett.85 (1988) 101–104.

    Article  PubMed  Google Scholar 

  96. Pfeffer, A. O., and Samson, H. H., Haloperidol and apomorphine effects on ethanol reinforcement in free feeding rats. Pharmac. Biochem. Behav.29 (1988) 343–350.

    Article  Google Scholar 

  97. Peura, P., Mackenzie, P., Koivusaari, U., and Lang, M., Increased fluidity of a model membrane caused by tetrahydro-β-carbolines. Molec. Pharmac.22 (1982) 721–724.

    Google Scholar 

  98. Peura, P., Airaksinen, M., Tuomisto, L., Saano, V., and Eriksson, C. J. P., L-methyl-tetrahydro-B-carboline in human blood after alcohol intake. Proc. Finn. Symp. Biol. Med. Eff. Alc. (1981) 1135.

  99. Privette, T. H., and Myers, R. D., Alcohol drinking: Role of neurotransmitter metabolites. Proc. natl Conf. Alc. Res. Raleigh, NC, 1987.

  100. Privette, T. H., Hornsby, R. L., and Myers, R. D., Buspirone alters alcohol drinking in rats by tetrahydropapaveroline injected into brain monoamine pathways. Alcohol5 (1988) 147–152.

    Article  PubMed  Google Scholar 

  101. Purvis, P. L., Hirst, M., and Baskerville, J. C., Voluntary ethanol consumption in the rat following peripheral administrations of 3-carboxysalsolinol. Subs. Alc. Actions/Misuse1 (1980) 439–445.

    Google Scholar 

  102. Rezvani, A. H., Mack, C. M., Crovi, S. I., and Myers, R. D., Central Ca++-channel blockade reverses ethanol-induced poikilothermia in the rat. Alcohol3 (1986) 273–279.

    Article  PubMed  Google Scholar 

  103. Richardson, J. S., and Novakovski, D. M., Brain monoamines and free choice ethanol consumption in rats. Drug Alc. Depend.3 (1978) 253–264.

    Article  Google Scholar 

  104. Rommelspacher, H., Buchau, C., and Weiss, J., Harman induces preference for ethanol in rats: Is the effect specific for ethanol. Pharmac. Biochem. Behav.26 (1987) 749–755.

    Article  Google Scholar 

  105. Rommelspacher, H., and Schmidt, L., Increased formation of β-carbolines in alcoholic patients following ingestion of ethanol. Pharmacopsychiatry18 (1985) 153–154.

    Google Scholar 

  106. Rommelspacher, H., and Subramanian, N., Tetrahydronorharmane modulates the depolarisation-induced efflux of 5-hydroxytryptamine and dopamine and is released by high potassium concentration from rat brain slices. Eur. J. Pharmac.56 (1979) 81–86.

    Article  Google Scholar 

  107. Rommelspacher, H., Damm, H., Strauss, S., and Schmidt, G., Ethanol induces an increase of harmane in the brain and urine of rats. Naunyn-Schmiedebergs Arch. Pharmak.327 (1984) 107–113.

    Article  Google Scholar 

  108. Russell, V. A., Lamm, M. C. L., and Taljaard, J. J. F., Effect of ethanol on [3H]dopamine release in rat nucleus accumbens and striatal slices. Neurochem. Res.13 (1988) 487–492.

    Article  PubMed  Google Scholar 

  109. Samson, H. H., Tolliver, G. D., Pfeffer, A. O., Sadeghi, K. G., and Mills, F. G., Oral ethanol reiforcement in the rat: Effect of the partial inverse benzodiazepine agonist Ro15-4513. Pharmac. Biochem. Behav.27 (1987) 517–519.

    Article  Google Scholar 

  110. Sandi, C., Borrell, J., and Guzaz, C., Naloxone decreases ethanol consumption within a free choice paradigm in rats. Pharmac. Biochem. Behav.29 (1988) 39–43.

    Article  Google Scholar 

  111. Sandler, M., Carter, S. B., Hunter, K. R., and Stern, G. M., Tetrahydroisoquinoline alkaloids: in vivo metabolites of L-dopa in man. Nature241 (1973) 439–443.

    PubMed  Google Scholar 

  112. Sandler, M., Glover, V., Armando, I., and Clow, A., Pictet-spengler condensation products, stress and alcoholism: some clinical overtones. Prog. clin. biol. Res.90 (1982) 215–226.

    PubMed  Google Scholar 

  113. Sasaoka, T., Kaneda, N., Niwa, T., Hashizume, Y., and Nagatsu, T., Analysis of salsolinol in human brain using high-performance liquid chromatography with electrochemical detection. J. Chromat.428 (1988) 152–155.

    Google Scholar 

  114. Schechter, M. D., Ability of 3-carboxysalsolinol to produce ethanol-like discrimination in rats. Psychopharmacology68 (1980) 277–281.

    Article  PubMed  Google Scholar 

  115. Signs, S. A., and Schechter, M. D., The role of dopamine and serotonin receptors in the mediation of the ethanol interoceptive cue. Pharmac. Biochem. Behav.30 (1988) 55–64.

    Article  Google Scholar 

  116. Sinclair, J. D., and Myers, R. D., Cerebroventricular tetrahydropapaveroline infusions and ethanol consumption in the rat. Subs. Alc. Actions/Misuse3 (1982) 5–24.

    Google Scholar 

  117. Sjöquist, B., Borg, S., and Kvande, H., Catecholamine derived compounds in urine and cerebrospinal fluid from alcoholics during and after long-standing intoxication. Subs. Alc. Actions/Misuse2 (1981) 63–72.

    Google Scholar 

  118. Sjöquist, B., Borg, S., and Kvande, H., Salsolinol and methylated salsolinol in urine and cerebrospinal fluid in healthy volunteers. Subs. Alc. Actions/Misuse2 (1981) 73–77.

    Google Scholar 

  119. Sjöquist, B., Johnson, H. A., and Borg, S., The influence of acute ethanol on the catecholamine system in man as reflected in cerebrospinal fluid and urine. A new condensation product, 1-carboxysalsolinol. Drug Alc. Depend.16 (1985) 241–249.

    Article  Google Scholar 

  120. Sjöquist, B., Liljequist, S., and Engel, J., Increased salsolinol levels in rat striatum and limbic forebrain following chronic ethanol treatment. J. Neurochem.39 (1982) 259–262.

    PubMed  Google Scholar 

  121. Sjöquist, B., Perdahl, E., and Winblad, B., The effect of alcoholism on salsolinol and biogenic amines in human brain. Drug. Alc. Depend.12 (1983) 15–23.

    Article  Google Scholar 

  122. Sjöquist, B., Eriksson, A., and Winblad, B., Salsolinol and catecholamines in human brain and their relation to alcoholism, in: β-Carbolines and Tetrahydroisoquinolines, pp. 57–67. Eds F. Bloom, J. Barchas, M. Sandler and E. Usdin. Alan Liss, New York 1982.

    Google Scholar 

  123. Suzdak, P. D., Paul, S. M., and Crawley, J. N., Effects of Ro15-4513 and other benzodiazepine receptor inverse agonists on alcohol-induced intoxication in the rat. J. Pharmac. expl Ther.245 (1988) 880–886.

    Google Scholar 

  124. Topel, H., Biochemical basis of alcoholism: Statements and hypotheses of present research. Alcohol2 (1985) 711–788.

    Article  PubMed  Google Scholar 

  125. Tuomisto, L., Airaksinen, M. M., Peura, P., and Eriksson, C. J. P., Alcohol drinking in the rat: increases following intracerebroventricular treatment with tetrahydro-β-carbolines. Pharmac. Biochem. Behav.17 (1982) 831–836.

    Article  Google Scholar 

  126. Weiner, H., Simpson, C. W., Thurman, J. A., and Myers, R. D., Disulfiram alters dopamine metabolism at sites in rat's forebrain as detected by push-pull perfusions. Brain Res. Bull.3 (1978) 541–548.

    Article  PubMed  Google Scholar 

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  1. Departments of Pharmacology and Psychiatric Medicine, School of Medicine, East Carolina University, 17834, Greenville, North Carolina, USA

    R. D. Myers

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Myers, R.D. Isoquinolines, beta-carbolines and alcohol drinking: Involvement of opioid and dopaminergic mechanisms. Experientia 45, 436–443 (1989). https://doi.org/10.1007/BF01952025

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Key words

  • Alcohol
  • brain
  • tetrahydropapaveroline
  • drinking
  • opiate receptors
  • dopamine
  • beta-carboline
  • aldehyde adducts
  • tetrahydroisoquinolines
  • ethanol