, Volume 65, Issue 2, pp 155–159 | Cite as

The involvemet of serotonergic neurons in the central nervous system as the possible mechanism for slow head-shaking behavior induced by methamphetamine in rats

  • Takeshi Honma
  • Hideaki Fukushima
Original Investigations


Following the IV administration of d-methamphetamine (MA), rats showed slow head shaking (SHS) and stereotyped gnawing (SG) behaviors in a dose-dependent manner. Methysergide, cyproheptadine, and p-chlorophenylalanine given intracerebroventricularly (ICV) or systemically significantly blocked SHS behavior induced by 10 mg/kg MA. Combined administration of l-5-hydroxytryptophan and peripheral decarboxlase inhibitor (Ro 4-4602) enhanced SHS behavior. Tyrosine hydroxylase inhibitor (H44/68) blocked SG behaviors, but dopamine-β-hydroxylase inhibitors (FLA 63 and U-14, 624) and combined administration of l-3,4-dihydroxyphenylalanine and Ro 4-4602 enhanced it. These drugs did not affect SHS behavior. Phentolamine, phenoxybenzamine, clonidine, isoproterenol, and propranolol given ICV or systemically showed no effect on either SHS or SG behaviors. These results suggest that SHS behavior is produced by the activation of serotonergic neurons in the central nervous system and are consistent with the view that SG behaviors are mediated through the release of dopamine. Some neuroleptics inhibited SHS as well as SG behaviors, but the order of inhibitory activity of neuroleptics on SHS behavior was quite different from their effects on SG behaviors induced by MA or apomorphine.

Key words

d-Methamphetamine Slow head shaking Stereotyped gnawing Serotonin Dopamine Neuroleptics 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 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. 9, 513–523 (1970)Google Scholar
  2. Boissier, J. R., Janssen, P. A. J., Julou, L., Loew, D. M., Møller Nielsen, I., Munkvad, I., Randrup, A., Stille, G., Tedeschi, D. H., van Rossum, J. M.: Pharmacology. In: The neuroleptics, D. P. Bobon, P. A. J. Janssen, J. Bobon, eds., pp. 23–70. Basel-München-Paris-New York: Karger 1970Google Scholar
  3. Carlsson, A.: Drugs acting through dopamine release. Pharmacol. Ther. (B) 1, 401–405 (1975)Google Scholar
  4. Corne, S. J., Pickering, R. W., Warner, B. T.: A method for assessing the effect of drugs on the central action of 5-hydroxytryptophan. Br. J. Pharmacol. 20, 106–120 (1963)Google Scholar
  5. De Groot, J.: The rat forebrain in stereotaxic coordinates. Amsterdam: N. V. Noord-Hollandsche Unitgevers Maatschappij 1963Google Scholar
  6. Dingell, J. V., Owens, M. L., Norvich, M. R., Sulser, F.: On the role of norepinephrine biosynthesis in the central action of amphetamine. Life Sci. 6, 1155–1162 (1967)Google Scholar
  7. Ernst, A. M., Smelik, P. G.: Site of action of dopamine and apomorphine on compulsive gnawing behavior in rats. Experimentia 22, 837–838 (1966)Google Scholar
  8. Guilleminault, C.: 5-HTP and the syndrome of intention or action myoclonus as a sequel to hypoxic encephalopathy. In: Serotonin and behavior, J. Barchas, E. Usdin, eds., pp. 443–452. New York-London: Academic 1973Google Scholar
  9. Henning, M., Rubenson, A.: Effects of 5-hydroxytryptophan on arterial blood pressure, body temperature and tissue monoamines in the rat. Acta Pharmacol. Toxicol. (Kbh.) 29, 145–154 (1971)Google Scholar
  10. Holmgren, B., Urba-Holmgren, R., Valdes, M.: Spontaneous and amphetamine induced head-shaking in infant rats. Pharmacol. Biochem. Behav. 5, 23–28 (1976)Google Scholar
  11. Honma, T., Sasajima, K., Ono, K., Kitagawa, S., Inaba, S., Yamamoto, H.: Synthesis and preliminary pharmacology of a novel butyrophenone derivative, ID-4708. Arzneim. Forsch. 24, 1248–1256 (1974)Google Scholar
  12. Honma, T., Fukushima, H.: Correlation between catalepsy and dopamine decrease in the rat striatum induced by neuroleptics. Neuropharmacology 15, 601–607 (1976)Google Scholar
  13. Honma, T., Kitagawa, S.: Effects of minor tranquilizers and neuroleptics on open-field behavior in rats. Folia Pharmacol. Jpn. 73, 337–345 (1977)Google Scholar
  14. Honma, T., Fukushima, H.: Role of brain norepinephrine in neuroleptic-induced catalepsy in rats. Pharmacol. Biochem. Behav. 7, 501–506 (1977)Google Scholar
  15. Honma, T.: Mechanism of methamphetamine toxicity in grouped mice and the effects of centrally acting drugs on its toxicity. Folia Pharmacol. Jpn. 74, 27–36 (1978)Google Scholar
  16. Honma, T., Fukushima, H.: Effects of bilateral lesions in the striatum or nucleus accumbens on the cataleptogenic activity of neuroleptics in rats. Jpn. J. Pharmacol. 28, 231–238 (1978)Google Scholar
  17. Johnson, G. A., Boukma, S. J., Kim, E. G.: In vivo inhibition of dopamine-β-hydroxylase by 1-phenyl-3-(2-thiazolyl)-2-thiourea (U-14624). J. Pharmacol. Exp. Ther. 171, 80–87 (1970)Google Scholar
  18. Koe, B. K., Weissman, A.: p-Chlorophenylalanine: A specific depletor of brain serotonin. J. Pharmacol. Exp. Ther. 154, 499–516 (1966)Google Scholar
  19. Langer, S. Z.: Presynaptic receptors and their role in the regulation of transmitter release. Br. J. Pharmacol. 60, 481–497 (1977)Google Scholar
  20. Leysen, J. E., Ladurn, P. M.: A serotonergic component of neuroleptic receptors. Arch. Int. Pharmacodyn. Ther. 230, 337–339 (1977)Google Scholar
  21. Litchfield, J. T., Wilcoxon, F.: A simplified method of evaluating dose-effect experiments. J. Pharmacol. Exp. Ther. 96, 99–113 (1949)Google Scholar
  22. Nakamura, M., Fukushima, H., Kitagawa, S.: Effect of amitriptyrine and isocarboxazide on 5-hydroxytryptophan induced head twitches in mice. Psychopharmacology 48, 101–104 (1976)Google Scholar
  23. Pletscher, A., Bartholini, G.: Selective rise in brain dopamine by inhibition of extracerebral levodopa decarboxylation. Clin. Pharmacol. Ther. 12, 344–352 (1971)Google Scholar
  24. Randrup, A., Munkvad, I.: Biochemical, anatomical and psychological investigations of stereotyped behavior induced by amphetamines. In: International symposium on amphetamines and related compounds, E. Costa, S. Garattini, eds., pp. 695–714. New York: Raven 1970Google Scholar
  25. Smith, C. B.: Enhancement by reserpine and α-methyl DOPA of the effects of d-amphetamine upon the locomotor activity of mice. J. Pharmacol. Exp. Ther. 142, 343–350 (1963)Google Scholar
  26. Stone, C. A., Wenger, H. C., Ludden, C. T., Stavorski, J. M., Rose, C. A.: Antiserotonin and antihistaminic properties of cyproheptadine. J. Pharmacol. Exp. Ther. 131, 73–84 (1961)Google Scholar
  27. Svensson, T. H.: The effect of inhibition of catecholamine synthesis on dexamphetamine-induced central stimulation. Eur. J. Pharmacol. 12, 161–166 (1970)Google Scholar
  28. Svensson, T. H.: Increased dopamine concentration in the striatum in the mouse by FLA 63, a dopamine-β-hydroxylase inhibitor. J. Pharm. Pharmacol. 25, 73–75 (1973)Google Scholar
  29. Thornberg, J. E., Moore, K. E.: The relative importance of dopaminergic and noradrenergic neuronal systems for the stimulation of locomotor activity induced by amphetamine and other drugs. Neuropharmacology 12, 853–866 (1973)Google Scholar
  30. Van Riezen, H.: Different central effects of the 5-HT antagonists mianserine and cyproheptadine. Arch. Int. Pharmacodyn. Ther. 198, 256–269 (1972)Google Scholar

Copyright information

© Springer-Verlag 1979

Authors and Affiliations

  • Takeshi Honma
    • 1
  • Hideaki Fukushima
    • 1
  1. 1.Research and Development Center, Pharmaceuticals DivisionSumitomo Chemical Co., Ltd.Takarazuka, HyogoJapan

Personalised recommendations