Caffeine pp 107-118 | Cite as

Effects of Caffeine on Monoamine Neurotransmitters in the Central and Peripheral Nervous System

  • J. D. Fernstrom
  • M. H. Fernstrom

Abstract

Over the past 10–15 years, interest in the behavioral and autonomic effects of caffeine has led neuropharmacologists, psychopharmacologists, and autonomic physiologists to explore for effects of this and related methylxanthines on the formation and release of neurotransmitters. Probably because of the availability of techniques and observed autonomic effects, most early studies focused on the catecholamines, and to a lesser extent on serotonin. In fact, the bulk of the neuropharmacologic literature on caffeine (which is small) considers effects related to these transmitters. Fewer and more recent studies have explored the possibility that caffeine effects may be mediated by other mechanisms, such as via an interaction with putative adenosine receptors. And only a handful of articles deal with effects of caffeine on such other transmitters as gamma-aminobutyric acid (GABA) and acetylcholine. For this reason, this review focuses primarily on the effects of caffeine on the monoamine neurotransmitters. Some information, however, is also presented on caffeine’s proposed effects on adenosine receptors, inasmuch as this is one possible route by which the methylxanthine exerts its actions on catecholamine neurons (as well as other cells). Reference to work on other transmitters is also made, but only in passing, to give the reader access to some of the available literature.

Keywords

Dopamine Morphine Adenosine Tryptophan Renin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Acheson KJ, Zahorska-Markiewicz B, Pittet P, Anantharaman K, Jequire E (1980) Caffeine and coffee: their influence on metabolic rate and substrate utilization in normal weight and obese individuals. Am J Clin Nutr 33: 989–997PubMedGoogle Scholar
  2. Ally AI, Nakatsu K (1976) Adenosine inhibition of isolated rabbit ileum and antagonism by theophylline. J Pharmacol Exp Ther 199: 208–215PubMedGoogle Scholar
  3. Anden NE, Jackson DM (1975) Locomotor activity stimulation in rats produced by dopamine in the nucleus accumbens: potentiation by caffeine. J Pharm Pharmacol 27: 666–670PubMedCrossRefGoogle Scholar
  4. Arnold MA, Fernstrom JD (1980) Administration of antisomatostatin serum to rats reverses the inhibition of pulsatile growth hormone secretion produced by an injection of metergoline, but not yohimbine. Neuroendocrinology 31: 194–199PubMedCrossRefGoogle Scholar
  5. Atuk, NO, Blaydes MC, Westervelt FB, Wood JE (1967) Effect of aminophylline on urinary excretion of epinephrine and norepinephrine in man. Circulation 35: 745–753PubMedGoogle Scholar
  6. Bellet S, Kershbaum A, Finck EM (1968) Response of free fatty acids to coffee and caffeine. Metabolism 17: 702–707PubMedCrossRefGoogle Scholar
  7. Bellet S, Roman L, DeCastro O, Kim KE, Kershbaum A (1969) Effect of coffee ingestion on catecholamine release. Metabolism 18: 288–291PubMedCrossRefGoogle Scholar
  8. Bellin JS, Sorrentino GM (1974) Activation of brain monoamine oxidase by some CNS depressants. Res Commun Chem Pathol Pharmacol 9: 673–680PubMedGoogle Scholar
  9. Berkowitz BA, Spector S (1971 a) The effect of caffeine and theophylline on the disposition of brain serotonin in the rat. Eur J Pharmacol 16: 322–325PubMedCrossRefGoogle Scholar
  10. Berkowitz BA, Spector S (1971 b) Effect of caffeine and theophylline on peripheral catecholamines. Eur J Pharmacol 13: 193–196PubMedCrossRefGoogle Scholar
  11. Berkowitz BA, Spector S (1973) The role of brain serotonin in the pharmacologic effects of the methyl xanthines. In: Barchas JD, Usdin E (eds) Serotonin and behavior. Academic, New York, pp 137–147Google Scholar
  12. Berkowitz BA, Tarver JH, Spector S (1970) Release of norepinephrine in the central nervous system by theophylline and caffeine. Eur J Pharmacol 10: 64–71PubMedCrossRefGoogle Scholar
  13. Carlsson A, Lindqvist M (1978) Dependence of 5-HT and catecholamine synthesis on concentrations of precursor amino acids in rat brain. Naunyn Schmiedebergs Arch Pharmacol 303: 157–164PubMedCrossRefGoogle Scholar
  14. Chiba S, Hashimoto K, Hashimoto K (1972) Pharmacological analysis of chromatographic responses of the S-A node to caffeine. Eur J Pharmacol 18: 116–120PubMedCrossRefGoogle Scholar
  15. Cohen Y, Lesne M, Valette G, Wepierre J (1970) Etude de l’interaction entre les xanthines et la noradrenaline 3H, au niveau du coeur isolé de rat. Biochem Pharmacol 19: 2117–2124PubMedCrossRefGoogle Scholar
  16. Cooper JR, Bloom FE, Roth RH (1982) The biochemical basis of neuropharmacology, 4th edn. Oxford, New YorkGoogle Scholar
  17. Corrodi H, Fuxe K, Jonsson G (1972) Effects of caffeine on central monoamine neurons. J Pharm Pharmacol 24: 155–158PubMedCrossRefGoogle Scholar
  18. Curzon G, Fernando JCR (1976) Effect of aminophylline on tryptophan and other aromatic amino acids in plasma, brain, and other tissues, and on brain 5-hydroxytryptamine metabolism. Br J Pharmacol 58: 533–545PubMedGoogle Scholar
  19. Daly JW, Bruns RF, Snyder SH (1981) Adenosine receptors in the central nervous system: relationship to the central action of methylxanthines. Life Sci 28: 2083–2097PubMedCrossRefGoogle Scholar
  20. DeGubareff T, Sleator W (1965) Effects of caffeine on mammalian atrial muscle and its interaction with adenosine and calcium. J Pharmacol Exp Ther 148: 202–214PubMedGoogle Scholar
  21. DeSchaepdryver AF (1959) Physio-pharmacological effects on suprarenal secretion of adrenaline and noradrenaline in dogs. Arch Int Pharmacodyn 119: 517–518Google Scholar
  22. Elmquist D, Feldman DS (1965) Calcium dependence of spontaneous acetylcholine release at mammalian motor nerve terminals. J Physiol (Lond) 181: 487–497Google Scholar
  23. Estler CJ (1979) Influence of pimozide on the locomotor hyperactivity produced by caffeine. J Pharm Pharmacol 31: 126–127PubMedCrossRefGoogle Scholar
  24. Fain JN, Li SY, Moreno FJ (1979) Regulation of cyclic AMP metabolism and lipolysis in isolated rat fat cells by insulin. N6-(phenylisopropyl)adenosine and 2’,5’-dideoxyadenosine. J Cyclic Nucleotide Res 5: 189–196PubMedGoogle Scholar
  25. Fernstrom MH, Bazil CW, Fernstrom JD (to be published) Lack of effect of caffeine injection on serotonin synthesis rate in rat brain.Google Scholar
  26. Fuxe K, Ungerstedt U (1974) Action of caffeine and theophylline on supersensitive dopamine receptors: considerable enhancement of receptor response to treatment with dopa and dopamine receptor agonists. Med Biol 52: 48–54PubMedGoogle Scholar
  27. Galloway MP, Roth RH (1982) Clonidine prevents methylxanthine stimulation of norepinephrine metabolism. Trans Am Soc Neurochem 13: 392Google Scholar
  28. Galloway MP, Roth RH (1983) Clonidine prevents methylxanthine stimulation of norepinephrine metabolism in rat brain. J Neurochem 40: 246–251PubMedCrossRefGoogle Scholar
  29. Geyer MA, Dawsey WJ, Mandell AJ (1975) Differential effects of caffeine, d-amphetamine, and methylphenidate on individual raphe cell fluorescence: a microspectrofluorimetric demonstration. Brain Res 85: 135–139PubMedCrossRefGoogle Scholar
  30. Galzigna L, Maina G, Rumney G (1971) Role of L-ascorbic acid in the reversal of the monoamine oxidase inhibition by caffeine. J Pharm Pharmacol 23: 303–305CrossRefGoogle Scholar
  31. Goldberg MR, Curatolo PW, Tung CS, Robertson D (1982) Caffeine down-regulates beta adre-noreceptors in rat forebrain. Neurosci Lett 31: 47–52PubMedCrossRefGoogle Scholar
  32. Grant S J, Redmond DE (1982) Methylxanthine activation of noradrenergic unit activity and reversal by Clonidine. Eur J Pharmacol 85: 105–109PubMedCrossRefGoogle Scholar
  33. Gysling K, Bustos G (1977) Effect of ethanol on dibutyryl cyclic adenosine monophosphate- and theophylline-induced stimulation of dopamine biosynthesis by rat striatal slices. Biochem Pharmacol 26: 559–562PubMedCrossRefGoogle Scholar
  34. Harris JE, Morgenroth VH, Roth RH, Baldessarini RJ (1974) Regulation of catecholamine biosynthesis in the rat brain in vitro by cyclic AMP. Nature 252: 156–158PubMedCrossRefGoogle Scholar
  35. Hedqvist P, Fredholm BB (1976) Effects of adenosine on adrenal neurotransmission: prejunctional inhibition and post-junctional enhancement. Naunyn Schmiedebergs Arch Pharmacol 293: 217–223PubMedCrossRefGoogle Scholar
  36. Hedqvist P, Fredholm BB, Olundh S (1978) Antagonistic effect of theophylline and adenosine on adrenergic neuroeffector transmission in the rabbit kidney. Circ Res 43: 592–598PubMedGoogle Scholar
  37. Higbee MD, Kumar M, Galant SP (1982) Stimulation of endogenous catecholamine release by theophylline: a proposed additional mechanism of action for theophylline effects. J Allergy Clin Immunol 70: 377–382PubMedCrossRefGoogle Scholar
  38. Hofmann WW (1969) Caffeine effects on transmitter depletion and mobilization at motor nerve terminals. Am J Physiol 216: 621–629PubMedGoogle Scholar
  39. Jhamandas K, Sawynok J, Sutak M (1978) Antagonism of morphine action on brain acetylcholine release by methylxanthines and calcium. Eur J Pharmacol 49: 309–312PubMedCrossRefGoogle Scholar
  40. Joyce EM, Koob GF(1981) Amphetamine-, scopolamine-, and caffeine-induced locomotor activity following 6-hydroxydopamine lesions of the mesolimbic dopamine system. Psychopharmacolo-gy (Berlin) 73: 311–313CrossRefGoogle Scholar
  41. Karasawa T, Furakawa K, Yoshida K, Shimizu M (1976) Effect of theophylline on monoamine metabolism in the rat brain. Eur J Pharmacol 37: 97–104PubMedCrossRefGoogle Scholar
  42. Levi L (1967) The effect of coffee on the function of the sympathoadrenomedullary system in man. Acta Med Scand 181: 431–438PubMedCrossRefGoogle Scholar
  43. Lin MT, Chandra A, Liu GG (1980) The effects of theophylline and caffeine on thermoregulatory functions of rats at different ambient temperatures. J Pharm Pharmacol 32: 204–208PubMedCrossRefGoogle Scholar
  44. Londos C, Cooper DMF, Schlegel W, Rodbell M (1978) Adenosine analogs inhibit adipocyte adenylate cyclase by a GTP-dependent process: basis for actions of adenosine and methylxanthines on cyclic AMP production and lipolysis. Proc Natl Acad Sci USA 75: 5362–5366PubMedCrossRefGoogle Scholar
  45. Lowenstein PR, Vacas MI, Cardinali DP (1982) Effect of pentoxifylline on alpha- and beta-adreno-ceptor sites in cerebral cortex, medial basal hypothalamus, and pineal gland of the rat. Neuropharmacology 21: 243–248PubMedCrossRefGoogle Scholar
  46. Marangos PJ, Paul SM, Parma AM, Goodwin FK, Syapin P, Skolnick P (1979) Purinergic inhibition of diazepam binding to rat brain (in vitro). Life Sci 24: 851–858PubMedCrossRefGoogle Scholar
  47. Martin JB (1976) Brain regulation of growth hormone secretion. In: Martini L, Ganong WF (eds) Frontiers in neuroendocrineology, vol 4. Raven, New York, pp 129–168Google Scholar
  48. Paalzow G, Paalzow L (1974) Theophylline increased sensitivity to nociceptive stimulation and regional turnover of rat brain 5-HT, noradrenaline and dopamine. Acta Pharmacol Toxicol (Co-penh) 34: 157–173CrossRefGoogle Scholar
  49. Peach MJ (1972) Stimulation of release of adrenal catecholamine by adenosine 3′: 5′-cyclic monophosphate and theophylline in the absence of extracellular Ca2+. Proc Natl Acad Sci USA 69: 834–836PubMedCrossRefGoogle Scholar
  50. Poisner AM (1973a) Caffeine-induced catecholamine secretion: similarity to caffeine-induced muscle contraction. Proc Soc Exp Biol Med 142: 103–105PubMedGoogle Scholar
  51. Poisner AM (1973 b) Direct stimulant effect of aminophylline on catecholamine release from the adrenal medulla. Biochem Pharmacol 22: 469–476PubMedCrossRefGoogle Scholar
  52. Polc P, Bonetti EP, Pieri L, Cumin R, Angioi RM, Mohler H, Haefely WE (1981) Caffeine antagonizes several central effects of diazepam. Life Sci 28: 2265–2275PubMedCrossRefGoogle Scholar
  53. Robertson D, Frolich JC, Carr K, Watson JT, Hollifield JW, Shand DG, Oates JA (1978) Effects of caffeine on plasma renin activity, catecholamines and blood pressure. N Engl J Med 298: 181–186PubMedCrossRefGoogle Scholar
  54. Sawynok J, Jhamandas KH (1976) Inhibition of acetylcholine release from cholinergic nerves by adenosine, adenine nucleotides, and morphine: antagonism by theophylline. J Pharmacol Exp Ther 197: 379–390PubMedGoogle Scholar
  55. Schlosberg AJ, Fernstrom JD, Kopczynski MC, Cusack BM, Gillis MA (1981) Acute effects of caffeine injection on neutral amino acids and brain monoamine levels in rats. Life Sci 29: 173–183PubMedCrossRefGoogle Scholar
  56. Scholfíeld CN (1982) Antagonism of gamma-aminobutyric acid and muscimol by Picrotoxin bicu-culline, strychnine, bemegride, leptazol, D-tubocurarine and theophylline in the isolated olfactory cortex. Naunyn Schmiedebergs Arch Pharmacol 318: 274–280PubMedCrossRefGoogle Scholar
  57. Scholtholt J, Nitz RE, Schraven E (1972) On the mechanism of the antagonistic action of xanthine derivatives against adenosine and coronary vasodilators. Arzneimittelforsch 22: 1255–1259PubMedGoogle Scholar
  58. Skok VI, Storch NN, Nishi S (1978) The effect of caffeine on the neurons of a mammalian sympathetic ganglion. Neuroscience 3: 697–708PubMedCrossRefGoogle Scholar
  59. Snider SR, Waldeck B (1974) Increased synthesis of adrenomedullary catecholamines induced by caffeine and theophylline. Naunyn Schmiedebergs Arch Pharmacol 281: 257–260PubMedCrossRefGoogle Scholar
  60. Snyder SH, Katims JJ, Annau Z, Bruns RF, Daly JW (1981) Adenosine receptors and behavioral actions of methylxanthines. Proc Natl Acad Sci USA 78: 3260–3264PubMedCrossRefGoogle Scholar
  61. Spindel E, Arnold M, Cusack B, Wurtman RJ (1980) Effects of caffeine on anterior pituitary and thyroid function in the rat. J Pharmacol Exp Ther 214: 58–62PubMedGoogle Scholar
  62. Strieker EM, Zimmerman MB, Friedman MI, Zigmond MJ (1977) Caffeine restores feeding response to 2-deoxy-D-glucose in 6-hydroxydopamine-treated rats. Nature 267: 174–175CrossRefGoogle Scholar
  63. Strubelt O (1969) The influence of reserpine, propranolol, and adrenal medullectomy on the hyperglycemic actions of theophylline and caffeine. Arch Int Pharmacodyn 179: 215–224PubMedGoogle Scholar
  64. Strubelt O, Siegers CP (1969) Zum Mechanismus der kalorigenen Wirkung von Theophyllin und Coffein. Biochem Pharmacol 18: 1207–1220PubMedCrossRefGoogle Scholar
  65. Sytinskii IA, Priyatkina TN (1966) Effect of certain drugs on the gamma-amino-butyric acid system of the central nervous system. Biochem Pharmacol 15: 49–54PubMedCrossRefGoogle Scholar
  66. Valzelli L, Bernasconi S (1973) Behavioral and neurochemical effects of caffeine in normal and aggressive mice. Pharmacol Biochem Behav 1: 251–254PubMedCrossRefGoogle Scholar
  67. Varagic VM, Zugic M (1971) Interactions of xanthine derivatives, catecholamines and glucose-6-phosphate on the isolated phrenic nerve diaphragm preparation of the rat. Pharmacology 5: 275–286PubMedCrossRefGoogle Scholar
  68. Vestal RE, Eiriksson CE, Musser B, Ozaki LK, Halter JB (1983) Effect of intravenous aminophylline on plasma levels of catecholamines and related cardiovascular and metabolic responses in man. Circulation 67: 162–171PubMedCrossRefGoogle Scholar
  69. Waldeck B (1971) Some effects of caffeine aminophylline on the turnover of catecholamines in the brain. J Pharm Pharmacol 23: 824–830PubMedCrossRefGoogle Scholar
  70. Waldeck B (1973) Sensitization by caffeine of central catecholamine receptors. J Neural Transm 34: 61–72PubMedCrossRefGoogle Scholar
  71. Waldeck B (1974) Ethanol and caffeine: a complex interaction with respect to locomotor activity and central catecholamines. Psychopharmacologia (Berlin) 36: 209–220CrossRefGoogle Scholar
  72. Wanatabe H, Ikeda M, Wanatabe K (1981) Properties of rotational behavior produced by methyl-xanthine derivatives in mice with unilateral striatal 6-hydroxydopamine-induced lesions. J Pharmacobiodyn 4: 301–307Google Scholar
  73. White BC, Simpson CC, Adams JE, Harkins D (1978) Monoamine synthesis and caffeine-induced locomotor activity. Neuropharmacology 17: 511–513PubMedCrossRefGoogle Scholar
  74. Wooten GF, Thoa, NB, Kopin IJ, Axelrod J (1973) Enhanced release of dopamine beta-hydroxylase and norepinephrine from sympathetic nerves by dibutyryl cyclic adenosine 3′,5′-mono-phosphate and theophylline. Mol Pharmacol 9: 178–183PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1984

Authors and Affiliations

  • J. D. Fernstrom
  • M. H. Fernstrom

There are no affiliations available

Personalised recommendations