Neurochemical Research

, Volume 18, Issue 12, pp 1329–1336 | Cite as

The potentiation of cortical neuron responses to noradrenaline by 2-phenylethylamine is independent of endogenous noradrenaline

  • I. A. Paterson
Original Articles


2-Phenylethylamine (PE) is an endogenous brain amine which produces sympathomimetic responses and potentiates cortical neuron responses to noradrenaline (NA). In order to examine further the mechanism of action of PE, extracellular recordings were made of the activity of single neurones in the cerebral cortex in urethane-anesthetized rats. Sympathomimetic responses to PE were blocked by pretreatment with reserpine, reserpine plus α-methyl-p-tyrosine and desipramine. It is concluded that the sympathomimetic responses to PE are indirect. 2-Phenylethylamine potentiated cortical neuron responses to electrical stimulation of the locus coeruleus in a dose-dependent manner. This was seen when PE was given systemically (with as little as 1 μg/kg) and iontophoretically. The effects of PE were not reproduced by its metabolite phenylacetic acid or its putative metabolite phenylethanolamine. Iontophoretic applications of PE (0–6 nA, 2–5 minutes) potentiated cortical neuron responses to iontophoretically applied NA, without affecting the spontaneous firing rate, or the responses to iontophoretically applied GABA or acetylcholine. This effect of PE was not blocked by pretreatment with α-methyl-p-tyrosine or desipramine, and was potentiated by pretreatment with reserpine and reserpine plus α-methyl-p-tyrosine. It is probable that the ability of PE to modulate neuronal responses to NA does not involve the presynaptic NA terminal or endogenous NA and it is likely that PE acts directly to increase the efficacy of NA. These findings are consistent with the hypothesis that the physiological role of PE is to modulate catecholaminergic transmission within the central nervous system.

Key Words

2-Phenylethylamine noradrenaline sympathomimetic response 


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  1. 1.
    Bertler, A. 1961. Effect of reserpine on the storage of catecholamines in brain and other tissues. Acta Physiol. Scand. 51:75–83.Google Scholar
  2. 2.
    Boulton, A. A. 1976. Cerebral aryl alkyl aminergic mechanisms. Pages 22–39in: Usdin, E., Sandler, M. (eds.) Trace Amines and the Brain, New York, Marcel Dekker.Google Scholar
  3. 3.
    Boulton, A. A. 1980. The trace amines: Neurohumours (cytosolic, pre- and/or postsynaptic, sinaptic, secondary, indirect). Behav. Brain Sci. 7:418.Google Scholar
  4. 4.
    Dourish, C. T. 1981. Behavioural effects of acute and chronic β-phenylethylamine administration in the rat: evidence for the involvement of 5-hydroxytryptamine. Neuropharmacol. 20:1067–1072.Google Scholar
  5. 5.
    Durden, D. A., Philips, S. R. and Boulton, A. A. 1973. Identification and distribution of β-phenylethylamine in the rat. Can. J. Biochem. 51:995–1002.Google Scholar
  6. 6.
    Dyck, L. E. 1983. Release of monoamines from striatal slices by phenelzine and β-phenylethylamine. Prog. Neuropsychopharmacol. Biol. Psychiat. 7:797–800.Google Scholar
  7. 7.
    Dyck, L. E. 1988. Release of some endogenous trace amines from rat striatal slices in the presence and absence of a monoamine oxidase inhibitor. In: Boulton, A. A., Juorio, A. V., Downer, R. G. H. eds. Trace Amines: Comparative and Clinical Neurobiology. Clifton NJ, Humana Press, 1988:223–237.Google Scholar
  8. 8.
    Dyck, L. E., Yang, C. R., Boulton, A. A. 1983. The biosynthesis ofptyramine,mtyramine, and β-phenylethylamine by rat striatal slices. J. Neurosci. Res. 10:211–220.Google Scholar
  9. 9.
    Fuxe, K., Grobecker, H.; Jonsson, J. 1967. The effect of β-phenylethylamine on central and peripheral monoamine containing neurones. Eur. J. Pharmacol. 2:202–207.Google Scholar
  10. 10.
    Harris, J., Trivedi, S., Ramakrishna, B. L. 1988. A contribution to the neuromodulatory/neurotransmitter role of trace amines. Pages 213–221in: Boulton, A. A.; Juorio, A. V.; Downer, R. G. H. eds.. Trace Amines: Comparative and Clinical Neurobiology, Clifton NJ, Humana Press.Google Scholar
  11. 11.
    Hauger, R. L., Skolnick, P., Paul, S. M. 1982. Specific (3H)-β-phenylethylamine binding sites in the rat brain. Eur. J. Pharmacol. 83:147–148.Google Scholar
  12. 12.
    Henwood, R. A., Boulton, A. A., Phillis, J. W. 1979. Iontophoretic studies of some trace amines in the mammalian CNS. Brain Res. 164:347–351.Google Scholar
  13. 13.
    Holzbauer, M., Vogt, M. 1956. Depression by reserpine of the noradrenaline concentration in the hypothalamus of the cat. J. Neurochem. 1:8–11.Google Scholar
  14. 14.
    Horn, A. D., Snyder, S. H. 1973. Steric requirements for catecholamine uptake by rat brain synaptosomes: studies with rigid analogues of amphetamine. J. Pharmacol. Exp. Ther. 180:523–530.Google Scholar
  15. 15.
    Jackson, D. M. 1978. β-Phenylethylamine studies on the mechanisms of its stimulant effects. Pages 289–313in: Mosnaim, A. D., Wolf, M. E. (eds.) Noncatecholic Phenylethylamines—Part 1 Phenylethylamine: Biological Mechanisms and Clinical Aspects. New York, Marcel Dekker.Google Scholar
  16. 16.
    Jackson, D. M. 1988. 2-Phenylethylamine, dopamine, and behaviour. Pages 429–432in: Sandler, M., Dahlström, A., Belmaker, R. H. (eds.) Progress in Catecholamine Research. Part B: Central Aspects, New York, Alan R Liss Inc.Google Scholar
  17. 17.
    Jones, R. S. G., Boulton, A. A. 1980. Interactions betweenptyramine,mtyramine or β-phenylethylamine and dopamine on single neurones in the cortex and caudate nucleus of the rat. Can. J. Physiol. Pharmacol. 58:222–227.Google Scholar
  18. 18.
    Juorio, A. V. 1988. Brain-β-phenylethylamine: Localization, Pathways, and Interrelation with Catecholamines. Pages 433–437in: Sandler, M., Dahlström, A., Belmaker, R. H. (eds.) Progress in Catecholamine Research. Part B: Central Aspects, New York, Alan R. Liss Inc..Google Scholar
  19. 19.
    Juorio, A. V., Greenshaw, A. J., Wishart, T. B. 1988. Reciprocal changes in striatal dopamine and β-phenylethylamine induced by reserpine in the presence of monoamine oxidase inhibitors. Naunyn-Schmiedeberg's Arch. Pharmacol. 338:644–648.Google Scholar
  20. 20.
    Karoum, F., Speciale S. G. J., Chuang, L. W., Wyatt, R. J. 1982. Selective effects of phenylethylamine on central catecholamines: a comparative study with amphetamine. J. Pharmacol. Exp. Ther. 223:432–439.Google Scholar
  21. 21.
    Li, X-M., Juorio, A. V., Paterson, I. A. and Boulton, A. A. 1992. Absence of 2-phenylethylamine binding after monoamine oxidase inhibition in rat brain. Eur. J. Pharmacol. 210:189–193.Google Scholar
  22. 22.
    Lundberg, P-A., Oreland, L., Engberg, G. 1985. Inhibition of locus coeruleus neuronal activity by β-pheylethylamine. Life Sci. 36:1889–1896.Google Scholar
  23. 23.
    Paterson, I. A. 1988. The potentiation of cortical neurone responses to noradrenaline by β-phenylethylamine effects of lesions of the locus coeruleus. Neurosci. Lett. 87:139–144.Google Scholar
  24. 24.
    Paterson, I. A., Boulton, A. A. 1988. β-Phenylethylamine enhances single cortical neurone responses to noradrenaline in the rat. Brain Res. Bull. 20:173–177.Google Scholar
  25. 25.
    Paterson, I. A., Hertz, I. 1989. Sodium-independent transport of noradrenaline in mouse and rat astrocytes in primary culture. J. Neurosci. Res. 23:71–77.Google Scholar
  26. 26.
    Paterson, I. A., Juorio, A. V. and Boulton, A. A. 1990. 2-Phenylethylamine: a modulator of catecholamine transmission in the mammalian central nervous system? J. Neurochem. 55:1827–1837.Google Scholar
  27. 27.
    Paterson, I. A., Juorio, A. V., Berry, M. D. and Zhu, M. Y. 1991. Inhibition of monoamine oxidase-B by (−)-deprenyl potentiates neuronal responses to dopamine agonists but does not inhibit dopamine catabolism in the rat striatum. J. Pharmacol. Exp. Ther. 258:1019–1026.Google Scholar
  28. 28.
    Paxinos, G., Watson, C. 1982. The Rat Brain in Stereotaxic Coordinates. New York, Academic Press.Google Scholar
  29. 29.
    Philips, S. R., Rozdilsky, B., Boulton, A. A. 1978. Evidence for the presence ofmtyramine,ptyramine, tryptamine and phenyethylamine in the rat brain and several areas of the human brain. Biol. Psychiat. 13:51–57.Google Scholar
  30. 30.
    Raiteri, M., Del Carmine, R., Bertollini, A., Levi, G. 1977. Effect of sympathomimetic amines on the synaptosomal transport of noradrenaline, dopamine and 5-hydroxytryptamine. Eur. J. Pharmacol. 41:133–143.Google Scholar
  31. 31.
    Reynolds, G. P., Sandler, M., Hardy, J., Bradford, H. 1980. The determination and distribution of 2-phenylethylamine in sheep brain. J. Neurochem. 34:1123–1125.Google Scholar
  32. 32.
    Sabelli, H. C., Vazquez, A. J., Flavin, D. 1975. Behavioural and electrophysiological effects of phenylethanolamine and 2-phenylethylamine. Psychopharmacol. 42:117–125.Google Scholar
  33. 33.
    Shannon, H. E., DeGregorio, C. M. 1982. Self-administration of the endogenous trace amines β-phenylethylamine, N-methylphenylethylamine and phenylethanolamine in dogs. J. Pharmacol. Exp. Ther. 222:52–60.Google Scholar
  34. 34.
    Sloviter, R. S., Conner, J. D., Drust, E. G. 1980. Serotonergic properties of β-phenylethylamine in rats. Neuropharmacol. 19:1071–1074.Google Scholar
  35. 35.
    Wu, P. H., Boulton, A. A. 1975. Metabolism, distribution and disappearance of injected β-phenylethylamine in the rat. Can. J. Biochem. 53:42–50.Google Scholar
  36. 36.
    Yu, P. H. 1986. Monoamine Oxidase. Pages 235–272in: Boulton, A. A., Baker, G. B., Yu, P. H. (eds.) Neuromethods, Volume 5, Neurotransmitter, Enzymes. Clifton, NJ, Humana Press.Google Scholar

Copyright information

© Plenum Publishing Corporation 1993

Authors and Affiliations

  • I. A. Paterson
    • 1
  1. 1.Neuropsychiatric Research Unit, Medical Research BuildingUniversity of SaskatchewanSaskatoonCanada

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