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. 1972 Sep;46(1):32–45. doi: 10.1111/j.1476-5381.1972.tb06846.x

On the role of central nervous system catecholamines and 5-hydroxytryptamine in the nialamide-induced behavioural syndrome

K Modigh, T H Svensson
PMCID: PMC1666113  PMID: 4263796

Abstract

1. Intraperitoneal administration of nialamide, 200 mg/kg, to mice elicited a pronounced increase in motor activity and rectal temperature concomitant with a gradual increase in the concentrations of 5-hydroxytryptamine (5-HT), noradrenaline (NA) and dopamine in the brain.

2. In mice treated with L-tryptophan, 300 mg/kg, 1 h before nialamide, the increase in motor activity appeared earlier than after nialamide alone, and the hyperthermia was more pronounced. The increase in 5-HT concentrations in the brain was more pronounced in these animals, whereas the concentrations of NA and dopamine were of the same magnitude as after nialamide alone.

3. Treatment with p-chlorophenylalanine methylester-HCl (PCPA), 400 mg/kg, 24 h before nialamide partially antagonized the increase in motor activity and the accumulation of NA and dopamine was not significantly different from that observed after nialamide alone.

4. Treatment with PCPA, 800 mg/kg, 72, 48 and 24 h before nialamide, completely antagonized the increase in motor activity and rectal temperature. The accumulation of brain 5-HT was greatly depressed in these animals. The concentrations of dopamine 1, 3 and 6 h and the concentration of NA 6 h after the nialamide injection were significantly lower in the mice given PCPA 800 mg/kg × 3, than in the mice given nialamide alone.

5. Administration of DL-5-hydroxytryptophan, 30 mg/kg, 1 h after the nialamide injection, to mice pretreated with PCPA, 800 mg/kg × 3, restored the increase in motor activity and rectal temperature.

6. L-Tryptophan, 300 mg/kg, given 1 h before nialamide to mice pretreated with PCPA, 800 mg/kg × 3, elicited a moderate increase in motor activity and a slight increase in the accumulation of 5-HT in the brain when compared to that after PCPA, 800 mg/kg × 3, and nialamide.

7. Administration of α-methyltyrosine methylester, 200 mg/kg, 2 h before nialamide partially antagonized the increase in motor activity and completely antagonized the increase in rectal temperature elicited by nialamide alone. The accumulation of brain NA and dopamine was inhibited in these animals.

8. It is concluded that the excitation in mice, elicited by nialamide, is mediated largely via brain 5-HT, but that also the brain catecholamines seem to contribute to this effect.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andén N. E., Corrodi H., Fuxe K. Hallucinogenic drugs of the indolealkylamine type and central monoamine neurons. J Pharmacol Exp Ther. 1971 Nov;179(2):236–249. [PubMed] [Google Scholar]
  2. Andén N. E., Corrodi H., Fuxe K., Hökfelt B., Hökfelt T., Rydin C., Svensson T. Evidence for a central noradrenaline receptor stimulation by clonidine. Life Sci. 1970 May 1;9(9):513–523. doi: 10.1016/0024-3205(70)90207-9. [DOI] [PubMed] [Google Scholar]
  3. Andén N. E., Magnusson T. An improved method for the fluorimetric determination of 5-hydroxytryptamine in tissues. Acta Physiol Scand. 1967 Jan-Feb;69(1):87–94. doi: 10.1111/j.1748-1716.1967.tb03493.x. [DOI] [PubMed] [Google Scholar]
  4. BERTLER A., CARLSSON A., ROSENGREN E. A method for the fluorimetric determination of adrenaline and noradrenaline in tissues. Acta Physiol Scand. 1958 Dec 15;44(3-4):273–292. doi: 10.1111/j.1748-1716.1958.tb01627.x. [DOI] [PubMed] [Google Scholar]
  5. CARLSSON A., DAHLSTROEM A., FUXE K., LINDQVIST M. HISTOCHEMICAL AND BIOCHEMICAL DETECTION OF MONOAMINE RELEASE FROM BRAIN NEURONS. Life Sci. 1965 Apr;4:809–816. doi: 10.1016/0024-3205(65)90313-9. [DOI] [PubMed] [Google Scholar]
  6. CARLSSON A., LINDQVIST M. In-vivo decarboxylation of alpha-methyl DOPA and alpha-methyl metatyrosine. Acta Physiol Scand. 1962 Jan;54:87–94. doi: 10.1111/j.1748-1716.1962.tb02331.x. [DOI] [PubMed] [Google Scholar]
  7. CARLSSON A., LINDQVIST M., MAGNUSSON T. 3,4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists. Nature. 1957 Nov 30;180(4596):1200–1200. doi: 10.1038/1801200a0. [DOI] [PubMed] [Google Scholar]
  8. CARLSSON A., WALDECK B. A fluorimetric method for the determination of dopamine (3-hydroxytyramine). Acta Physiol Scand. 1958 Dec 15;44(3-4):293–298. doi: 10.1111/j.1748-1716.1958.tb01628.x. [DOI] [PubMed] [Google Scholar]
  9. Corrodi H. Blockade of the psychotic syndrome caused by nialamide in mice. J Pharm Pharmacol. 1966 Mar;18(3):197–199. doi: 10.1111/j.2042-7158.1966.tb07852.x. [DOI] [PubMed] [Google Scholar]
  10. FELDBERG W., MYERS R. D. A NEW CONCEPT OF TEMPERATURE REGULATION BY AMINES IN THE HYPOTHALAMUS. Nature. 1963 Dec 28;200:1325–1325. doi: 10.1038/2001325a0. [DOI] [PubMed] [Google Scholar]
  11. FELDBERG W., MYERS R. D. EFFECTS ON TEMPERATURE OF AMINES INJECTED INTO THE CEREBRAL VENTRICLES. A NEW CONCEPT OF TEMPERATURE REGULATION. J Physiol. 1964 Sep;173:226–231. doi: 10.1113/jphysiol.1964.sp007454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fibiger H. C., Campbell B. A. The effect of para-chlorophenylalanine on spontaneous locomotor activity in the rat. Neuropharmacology. 1971 Jan;10(1):25–32. doi: 10.1016/0028-3908(71)90005-0. [DOI] [PubMed] [Google Scholar]
  13. Fuxe K., Butcher L. L., Engel J. DL-5-hydroxytryptophan-induced changes in central monoamine neurons after peripheral decarboxylase inhibition. J Pharm Pharmacol. 1971 Jun;23(6):420–424. doi: 10.1111/j.2042-7158.1971.tb08673.x. [DOI] [PubMed] [Google Scholar]
  14. Grahame-Smith D. G. Studies in vivo on the relationship between brain tryptophan, brain 5-HT synthesis and hyperactivity in rats treated with a monoamine oxidase inhibitor and L-tryptophan. J Neurochem. 1971 Jun;18(6):1053–1066. doi: 10.1111/j.1471-4159.1971.tb12034.x. [DOI] [PubMed] [Google Scholar]
  15. HESS S. M., DOEPFNER W. Behavioral effects and brain amine content in rats. Arch Int Pharmacodyn Ther. 1961 Nov 1;134:89–99. [PubMed] [Google Scholar]
  16. Hornykiewicz O. Dopamine (3-hydroxytyramine) and brain function. Pharmacol Rev. 1966 Jun;18(2):925–964. [PubMed] [Google Scholar]
  17. Jéquier E., Lovenberg W., Sjoerdsma A. Tryptophan hydroxylase inhibition: the mechanism by which p-chlorophenylalanine depletes rat brain serotonin. Mol Pharmacol. 1967 May;3(3):274–278. [PubMed] [Google Scholar]
  18. Koe B. K. Tryptophan hydroxylase inhibitors. Fed Proc. 1971 May-Jun;30(3):886–896. [PubMed] [Google Scholar]
  19. Koe B. K., Weissman A. p-Chlorophenylalanine: a specific depletor of brain serotonin. J Pharmacol Exp Ther. 1966 Dec;154(3):499–516. [PubMed] [Google Scholar]
  20. Lomax P. Drugs and body temperature. Int Rev Neurobiol. 1970;12:1–43. doi: 10.1016/s0074-7742(08)60057-4. [DOI] [PubMed] [Google Scholar]
  21. McGeer E. G., Peters D. A., McGeer P. L. Inhibition of rat brain tryptophan hydroxylase by 6-halotryptophans. Life Sci. 1968 Jun 15;7(12):605–615. doi: 10.1016/0024-3205(68)90082-9. [DOI] [PubMed] [Google Scholar]
  22. Modigh K. Central and peripheral effects of 5-hydroxytryptophan on motor activity in mice. Psychopharmacologia. 1972;23(1):48–54. doi: 10.1007/BF00414413. [DOI] [PubMed] [Google Scholar]
  23. Persson T. Drug induced changes in 3H-catholamine accumulation after 3H-tyrosine. Acta Pharmacol Toxicol (Copenh) 1970;28(5):378–390. doi: 10.1111/j.1600-0773.1970.tb00564.x. [DOI] [PubMed] [Google Scholar]
  24. Pirch J. H. Stimulation of locomotor activity by p-chlorophenylalanine and a low dose of reserpine. Arch Int Pharmacodyn Ther. 1969 Oct;181(2):434–440. [PubMed] [Google Scholar]
  25. Pletscher A. Monoamine oxidase inhibitors. Pharmacol Rev. 1966 Mar;18(1):121–129. [PubMed] [Google Scholar]
  26. ROWE R. P., BLOOM B. M., PAN S. Y., FINGER K. F. Pharmacological studies with nialamide, a new antidepressant agent. Proc Soc Exp Biol Med. 1959 Aug-Sep;101:832–836. doi: 10.3181/00379727-101-25112. [DOI] [PubMed] [Google Scholar]
  27. Svensson T. H. On the role of central noradrenaline in the regulation of motor activity and body temperature in the mouse. Naunyn Schmiedebergs Arch Pharmakol. 1971;271(1):111–120. doi: 10.1007/BF01002176. [DOI] [PubMed] [Google Scholar]
  28. Svensson T. H., Thieme G. An investigation of a new instrument to measure motor activity of small animals. Psychopharmacologia. 1969;14(2):157–163. doi: 10.1007/BF00403689. [DOI] [PubMed] [Google Scholar]
  29. Svensson T. H., Waldeck B. On the relation between motor activity and the degree of enzyme inhibition following inhibition of tyrosine hydroxylase. Acta Pharmacol Toxicol (Copenh) 1971;29(1):60–64. doi: 10.1111/j.1600-0773.1971.tb00582.x. [DOI] [PubMed] [Google Scholar]
  30. Svensson T. H., Waldeck B. On the role of brain catecholamines in motor activity: experiments with inhibitors of synthesis and of monoamine oxidase. Psychopharmacologia. 1970;18(4):357–365. doi: 10.1007/BF00402762. [DOI] [PubMed] [Google Scholar]
  31. Svensson T. H., Waldeck B. On the significance of central noradrenaline for motor activity: experiments with a new dopamine beta-hydroxylase inhibitor. Eur J Pharmacol. 1969 Sep;7(3):278–282. doi: 10.1016/0014-2999(69)90092-2. [DOI] [PubMed] [Google Scholar]
  32. Tenen S. S. The effects of p-chlorophenylalanine, a serotonin depletor, on avoidance acquisition, pain sensitivity and related behavior in the rat. Psychopharmacologia. 1967;10(3):204–219. doi: 10.1007/BF00401382. [DOI] [PubMed] [Google Scholar]
  33. Volicer L. Correlation between behavioral and biochemical effects of p-chlorophenylalanine in mice and rats. Int J Neuropharmacol. 1969 Jul;8(4):361–364. doi: 10.1016/0028-3908(69)90022-7. [DOI] [PubMed] [Google Scholar]
  34. Welch A. S., Welch B. L. Effect of p-chlorophenylalanine on brain noradrenaline in mice. J Pharm Pharmacol. 1967 Sep;19(9):632–633. doi: 10.1111/j.2042-7158.1967.tb09607.x. [DOI] [PubMed] [Google Scholar]

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