Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1976 Jan;56(1):77–85. doi: 10.1111/j.1476-5381.1976.tb06961.x

Effects of drugs acting on cerebral 5-hydroxytryptamine mechanisms on dopamine-dependent turning behaviour in mice.

J A Milson, C J Pycock
PMCID: PMC1666754  PMID: 130178

Abstract

1. The effects of drugs acting on cerebral 5-hydroxytryptaminergic mechanisms on drug-induced turning behaviour in mice with unilateral destruction of nigro-striatal dopaminergic nerve terminals have been studied. 2. Administration of L-tryptophan (400 mg/kg) or 5-hydroxytryptophan (200 mg/kg) increased brain 5-hydroxytryptamine and decreased the turning induced by both apomorphine (2 mg/kg) and amphetamine (5 mg/kg). 3. Parachlorophenylalanine (3 X 500 mg/kg) decreased brain 5-hydroxytryptamine and increased both apomorphine and amphetamine-induced circling behaviour. 4. Varying the protein content of dietary intake significantly altered brain 5-hydroxytryptamine and tryptophan levels, spontaneous locomotor activity and amphetamine-induced circling behaviour in these mice. 5. Systemic administration of methysergide (0.5-4 mg/kg), lysergic acid diethylamide (0.025-0.2 mg/kg), cyproheptadine (2.5-20 mg/kg) or clomipramine (0.6-20 mg/kg) produced no consistent effect on drug-induced turning behaviour. 6. The results suggest that circling behaviour due to striatal dopamine receptor stimulation is depressed by an elevation of brain 5-hydroxytryptamine and enhanced by a reduction in brain 5-hydroxytryptamine. 7. The possible physiological relationship between dopamine and 5-hydroxytryptamine neurones in the basal ganglia is discussed.

Full text

PDF
77

Selected References

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

  1. Aghajanian G. K. LSD and CNS transmission. Annu Rev Pharmacol. 1972;12:157–168. doi: 10.1146/annurev.pa.12.040172.001105. [DOI] [PubMed] [Google Scholar]
  2. Andén N. E., Corrodi H., Fuxe K., Hökfelt T. Evidence for a central 5-hydroxytryptamine receptor stimulation by lysergic acid diethylamide. Br J Pharmacol. 1968 Sep;34(1):1–7. doi: 10.1111/j.1476-5381.1968.tb07943.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Andén N. E., Dahlström A., Fuxe K., Larsson K. Functional role of the nigro-neostriatal dopamine neurons. Acta Pharmacol Toxicol (Copenh) 1966;24(2):263–274. doi: 10.1111/j.1600-0773.1966.tb00389.x. [DOI] [PubMed] [Google Scholar]
  4. Ashkenazi R., Holman R. B., Vogt M. Release of transmitters on stimulation of the nucleus linearis raphe in the cat. J Physiol. 1972 May;223(1):255–259. doi: 10.1113/jphysiol.1972.sp009845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bak I. J., Choi W. B., Hassler R., Usunoff K. G., Wagner A. Fine structural synaptic organization of the corpus striatum and substantia nigra in rat and cat. Adv Neurol. 1975;9:25–41. [PubMed] [Google Scholar]
  6. Baldessarini R. J., Amatruda T. T., 3rd, Griffith F. F., Gerson S. Differential effects of serotonin on turning and sterotypy induced by apomorphine. Brain Res. 1975 Jul 25;93(1):158–163. doi: 10.1016/0006-8993(75)90295-4. [DOI] [PubMed] [Google Scholar]
  7. Besson M. J., Cheramy A., Feltz P., Glowinski J. Release of newly synthesized dopamine from dopamine-containing terminals in the striatum of the rat. Proc Natl Acad Sci U S A. 1969 Mar;62(3):741–748. doi: 10.1073/pnas.62.3.741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bieger D., Larochelle L., Hornykiewicz O. A model for the quantitative study of central dopaminergic and serotoninergic activity. Eur J Pharmacol. 1972 Apr;18(1):128–136. doi: 10.1016/0014-2999(72)90140-9. [DOI] [PubMed] [Google Scholar]
  9. Biggio G., Fadda F., Fanni P., Tagliamonte A., Gessa G. L. Rapid depletion of serum tryptophan, brain tryptophan, serotonin and 5-hydroxyindoleacetic acid by a tryptophan-free diet. Life Sci. 1974 Apr 1;14(7):1321–1329. doi: 10.1016/0024-3205(74)90440-8. [DOI] [PubMed] [Google Scholar]
  10. Boakes R. J., Bradley P. B., Briggs I., Dray A. Antagonism of 5-hydroxytryptamine by LSD 25 in the central nervous system: a possible neuronal basis for the actions of LSD 25. Br J Pharmacol. 1970 Oct;40(2):202–218. doi: 10.1111/j.1476-5381.1970.tb09914.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Breese G. R., Cooper B. R., Mueller R. A. Evidence for involvement of 5-hydroxytryptamine in the actions of amphetamine. Br J Pharmacol. 1974 Oct;52(2):307–314. doi: 10.1111/j.1476-5381.1974.tb09714.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Butcher L. L., Engel J., Fuxe K. Behavioral, biochemical, and histochemical analyses of the central effects of monoamine precursors after peripheral decarboxylase inhibition. Brain Res. 1972 Jun 22;41(2):387–411. doi: 10.1016/0006-8993(72)90510-0. [DOI] [PubMed] [Google Scholar]
  13. CHANG C. C. A SENSITIVE METHOD FOR SPECTROPHOTOFLUOROMETRIC ASSAY OF CATECHOLAMINES. Int J Neuropharmacol. 1964 Dec;3:643–649. doi: 10.1016/0028-3908(64)90089-9. [DOI] [PubMed] [Google Scholar]
  14. Campbell B. A., Fibiger H. C. Potentiation of amphetamine-induced arousal by starvation. Nature. 1971 Oct 8;233(5319):424–425. doi: 10.1038/233424a0. [DOI] [PubMed] [Google Scholar]
  15. Carlsson A., Corrodi H., Fuxe K., Hökfelt T. Effect of antidepressant drugs on the depletion of intraneuronal brain 5-hydroxytryptamine stores caused by 4-methyl-alpha-ethyl-meta-tyramine. Eur J Pharmacol. 1969 Mar;5(4):357–366. doi: 10.1016/0014-2999(69)90113-7. [DOI] [PubMed] [Google Scholar]
  16. Chase T. N., Breese G. R., Kopin I. J. Serotonin release from brain slices by electrical stimulation: regional differences and effect of LSD. Science. 1967 Sep 22;157(3795):1461–1463. doi: 10.1126/science.157.3795.1461. [DOI] [PubMed] [Google Scholar]
  17. Costall B., Naylor R. J. Stereotyped and circling behaviour induced by dopaminergic agonists after lesions of the midbrain raphe nuclei. Eur J Pharmacol. 1974 Dec;29(2):206–222. doi: 10.1016/0014-2999(74)90019-3. [DOI] [PubMed] [Google Scholar]
  18. DOEPFNER W. Biochemical observations on LSD-25 and Deseril. Experientia. 1962 Jun 15;18:256–257. doi: 10.1007/BF02148217. [DOI] [PubMed] [Google Scholar]
  19. Denckla W. D., Dewey H. K. The determination of tryptophan in plasma, liver, and urine. J Lab Clin Med. 1967 Jan;69(1):160–169. [PubMed] [Google Scholar]
  20. Fernstrom J. D., Wurtman R. J. Brain serotonin content: physiological regulation by plasma neutral amino acids. Science. 1972 Oct 27;178(4059):414–416. doi: 10.1126/science.178.4059.414. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Fuxe K., Hökfelt T., Ungerstedt U. Localization of indolealkylamines in CNS. Adv Pharmacol. 1968;6(Pt A):235–251. doi: 10.1016/s1054-3589(08)61177-1. [DOI] [PubMed] [Google Scholar]
  23. Grabowska M., Antkiewicz L., Maj J., Michaluk J. Apomorphine and central serotonin neurons. Pol J Pharmacol Pharm. 1973 Jan-Feb;25(1):29–39. [PubMed] [Google Scholar]
  24. Grabowska M. Influence of midbrain raphe lession on some pharmacological and biochemical effects of apomorphine in rats. Psychopharmacologia. 1974;39(4):315–322. doi: 10.1007/BF00422971. [DOI] [PubMed] [Google Scholar]
  25. Grabowska M., Michaluk J. On the role of serotonin in apomorphine-induced locomotor stimulation in rats. Pharmacol Biochem Behav. 1974 Mar-Apr;2(2):263–266. doi: 10.1016/0091-3057(74)90063-x. [DOI] [PubMed] [Google Scholar]
  26. Hadzović S., Ernst A. M. The effect of 5-hydroxytryptamine and 5-hydroxytryptophan on extra-pyramidal function. Eur J Pharmacol. 1969 May;6(2):90–95. doi: 10.1016/0014-2999(69)90202-7. [DOI] [PubMed] [Google Scholar]
  27. Holman R. B., Vogt M. Release of 5-hydroxytryptamine from caudate nucleus and septum. J Physiol. 1972 May;223(1):243–254. doi: 10.1113/jphysiol.1972.sp009844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Jacobs B. L. Effect of two dopamine receptor blockers on a serotonin-mediated behavioral syndrome in rats. Eur J Pharmacol. 1974 Aug;27(3):363–366. doi: 10.1016/0014-2999(74)90014-4. [DOI] [PubMed] [Google Scholar]
  29. Jacobs B. L., Eubanks E. E., Wise W. D. Effect of indolealkylamine manipulations on locomotor activity in rats. Neuropharmacology. 1974 Jul;13(7):575–583. doi: 10.1016/0028-3908(74)90045-8. [DOI] [PubMed] [Google Scholar]
  30. Kim J. S., Hassler R., Kurokawa M., Bak I. J. Abnormal movements and rigidity induced by harmaline in relation to striatal acetylcholine, serotonin, and dopamine. Exp Neurol. 1970 Nov;29(2):189–200. doi: 10.1016/0014-4886(70)90049-x. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. LAVERTY R., SHARMAN D. F. THE ESTIMATION OF SMALL QUANTITIES OF 3,4-DIHYDROXYPHENYLETHYLAMINE IN TISSUES. Br J Pharmacol Chemother. 1965 Apr;24:538–548. doi: 10.1111/j.1476-5381.1965.tb01744.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Lewander T. Influence of various psychoactive drugs on the in vivo metabolism of d-amphetamine in the rat. Eur J Pharmacol. 1969 Apr;6(1):38–44. doi: 10.1016/0014-2999(69)90062-4. [DOI] [PubMed] [Google Scholar]
  34. Maickel R. P., Cox R. H., Jr, Saillant J., Miller F. P. A method for the determination of serotonin and norepinephrine in discrete areas of rat brain. Int J Neuropharmacol. 1968 May;7(3):275–281. doi: 10.1016/0028-3908(68)90034-8. [DOI] [PubMed] [Google Scholar]
  35. 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]
  36. Modigh K. Effects of L-tryptophan on motor activity in mice. Psychopharmacologia. 1973 May 21;30(2):123–134. doi: 10.1007/BF00421427. [DOI] [PubMed] [Google Scholar]
  37. Modigh K. Effects of isolation and fighting in mice on the rate of synthesis of noradrenaline, dopamine and 5-hydroxytryptamine in the brain. Psychopharmacologia. 1973 Oct 23;33(1):1–17. doi: 10.1007/BF00428790. [DOI] [PubMed] [Google Scholar]
  38. Modigh K. Functional aspects of 5-hydroxytryptamine turnover in the central nervous system. Acta Physiol Scand Suppl. 1974;403:1–56. [PubMed] [Google Scholar]
  39. Ng L. K., Chase T. N., Colburn R. W., Kopin I. J. Release of ( 3 H)dopamine by L-5-hydroxytryptophan. Brain Res. 1972 Oct 27;45(2):499–505. doi: 10.1016/0006-8993(72)90478-7. [DOI] [PubMed] [Google Scholar]
  40. Parizek J., Hassler R., Bak I. J. Light and electron microscopic autoradiography of substantia nigra of rat after intraventricular administration of tritium labelled norepinephrine, dopamine, serotonin and the precursors. Z Zellforsch Mikrosk Anat. 1971;115(1):137–148. doi: 10.1007/BF00330222. [DOI] [PubMed] [Google Scholar]
  41. Pieri L., Pieri M., Haefely W. LSD as an agonist of dopamine receptors in the striatum. Nature. 1974 Dec 13;252(5484):586–588. doi: 10.1038/252586a0. [DOI] [PubMed] [Google Scholar]
  42. Poirier L. J., Singh P., Boucher R., Bouvier G., Olivier A., Larochelle P. Effect of brain lesions on striatal monoamines in the cat. Arch Neurol. 1967 Dec;17(6):601–608. doi: 10.1001/archneur.1967.00470300043008. [DOI] [PubMed] [Google Scholar]
  43. Pycock C., Anlezark G. Letter: LSD and dopamine receptors. Nature. 1975 Sep 4;257(5521):69–70. doi: 10.1038/257069c0. [DOI] [PubMed] [Google Scholar]
  44. Shaskan E. G., Snyder S. H. Kinetics of serotonin accumulation into slices from rat brain: relationship to catecholamine uptake. J Pharmacol Exp Ther. 1970 Nov;175(2):404–418. [PubMed] [Google Scholar]
  45. Simpson L. L. A study of the interaction between amphetamine and food deprivation. Psychopharmacologia. 1974;38(4):279–286. doi: 10.1007/BF00429126. [DOI] [PubMed] [Google Scholar]
  46. Tuck J. R., Punell G. Uptake of (3H)5-hydroxytryptamine and (3H)noradrenaline by slices of rat brain incubated in plasma from patients treated with chlorimipramine, imipramine or amitroptyline. J Pharm Pharmacol. 1973 Jul;25(7):573–574. doi: 10.1111/j.2042-7158.1973.tb09160.x. [DOI] [PubMed] [Google Scholar]
  47. Ungerstedt U. Postsynaptic supersensitivity after 6-hydroxy-dopamine induced degeneration of the nigro-striatal dopamine system. Acta Physiol Scand Suppl. 1971;367:69–93. doi: 10.1111/j.1365-201x.1971.tb11000.x. [DOI] [PubMed] [Google Scholar]
  48. 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]
  49. Von Voigtlander P. F., Moore K. E. Turning behavior of mice with unilateral 6-hydroxydopamine lesions in the striatum: effects of apomorphine, L-DOPA, amanthadine, amphetamine and other psychomotor stimulants. Neuropharmacology. 1973 May;12(5):451–462. doi: 10.1016/0028-3908(73)90061-0. [DOI] [PubMed] [Google Scholar]
  50. Weiner W. J., Goetz C., Klawans H. L. Serotonergic and antiserotonergic influences on apomorphine-induced stereotyped behaviour. Acta Pharmacol Toxicol (Copenh) 1975 Feb;36(2):155–160. doi: 10.1111/j.1600-0773.1975.tb00781.x. [DOI] [PubMed] [Google Scholar]
  51. Weiner W. J., Goetz C., Westheimer R., Klawans H. L., Jr Serotonergic and antiserotonergic influences on amphetamine-induced stereotyped behavior. J Neurol Sci. 1973 Dec;20(4):373–379. doi: 10.1016/0022-510x(73)90171-8. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES