Head-Twitch Response Induced by ρ-Hydroxyamphetamine in Mice

  • Kensuke Kisara
  • Takeshi Tadano
  • Shinetsu Satoh
  • Hiroyasu Kinemuchi


P-Hydroxyamphetamine (p-OHA) is an indirectly acting sympathomimetic amine which is of particularly pharmacological significance, because it is a major metabolite of amphetamine in most species examined. It is well known that amphetamine causes clinical hallucination. It is not yet clear, however, whether amphetamine or its metabolite elicites such effect. Head-twitch response (HTR) has been regarded as an experimental model for hallucination and recently we observed that p-OHA markedly induced HTR in mice. The present work was undertaken to study possible participation of a serotonergic system in the mechanism of HTR induced by p-OHA. HTR induced by intracerebroventricular (i.c.v.) injection of p-OHA continued for 20–80 min and its peak time was found to be approximately 30–40 min after the administration of p-OHA. The i.c.v. administartion of p-OHA dose-dependently induced HTR. Pretreatment with reserpine (1 mg/kg × 3, i.p.) significantly potentiated HTR induced by p-OHA. Pretreatment with serotonin (10 μg/mouse, i.c.v.) caused 2–2.5 fold increase in HTR, compared to the saline control. Pretreatment with p-chlorophenylalanine (200 mg/kg, i.p.), in contrast, reduced HTR, as did pretreatment with cyproheptadine, dimethothiazine, or morphine. These results suggest that HTR produced by p-OHA may involve the serotonergic system in the brain and this system may exert an excitatory effect on HTR.


Serotonergic System Spontaneous Motor Acti Ethanol Withdrawal Sympathomimetic Amine Head Twitch 
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  1. Brittain R. T. and Handley S.L. (1967) Temperature changes produced by the injection of catecholamines and 5-hydroxytryptamine into the cerebral ventricles of the conscious mouse. J. Physiol. 192, 805–813.PubMedGoogle Scholar
  2. Collier H.O.J., Hammond M.D. and Schneider C. (1974) Biogenic amines and head twitches in mice during ethanol withdrawal. Br. J. Pharmacol. 51, 310–311.PubMedGoogle Scholar
  3. Corne S.J., Pickering R.W. and Warner B.T. (1963) A method for assessing the effects of drugs on the central actions of 5-hydroxytryptamine. Br. J. Pharmacol. 20, 106–120.Google Scholar
  4. Corne S.J. and Pickering R.W. (1967) A possible correlation between drug-induced hallucinations in man and a behavioural response in mice. Psychopharmacol. 11, 65–78.CrossRefGoogle Scholar
  5. Jori A. and Caccia S. (1974) Distribution of amphetamine and its hydroxylated metabolites in various areas of the rat brain. J. Pharm. Pharmacol. 26, 74.6–748.Google Scholar
  6. Keller D.L. and Umbreit W.W. (1956) “Permanent” Alteration of behavior in mice by chemical and psychological means. Science 124, 723–724.PubMedCrossRefGoogle Scholar
  7. Lewander T. (1971) Displacement of brain and heart noradrenaline by p-hydroxynorephedrine after administration of p-hydroxyamphetamine. Acta Pharmacol. Toxicol. 29, 20–32.Google Scholar
  8. Malick J.B., Doren E. and Barnett A. (1977) Quipazine-induced head-twitch in mice. Pharmacol. Biochem. Behavior 6, 325–329.CrossRefGoogle Scholar
  9. Moore K.E. (1964) The role of endogenous norepinephrine in the toxicity of d-amphetamine in aggregated mice. J. Pharmacol. Exp. Ther. 144, 45–51.PubMedGoogle Scholar
  10. Nakamura M. and Fukushima H. (1978) Effects of reserpine, para-chlorophenylalanine, 5,6-dihydroxytryptamine and fludiazepam on the head twitches induced by 5-hydroxytryptamine or 5-methoxytryptamine in mice. J. Pharm. Pharmacol. 30, 254–256.PubMedCrossRefGoogle Scholar
  11. Orikasa S., Sakurada S. and Kisara K. (1980) Head-twitch response induced by tyramine. Psychopharmacol. 67, 53–59.CrossRefGoogle Scholar
  12. Randrup A. and Munkvad I. (1966) Role of catecholamines in the amphetamine excitatory response. Nature 211, 540.PubMedCrossRefGoogle Scholar
  13. Randrup A. and Munkvad I. (1970) Biochemical, anatomical and psychological investigations of stereotyped behavior induced by amphetamines. In: International symposium on amphatamines and related compounds. Ed: E. Costa and S. Garattini. Raven Press. New York.Google Scholar
  14. Ross S.B. and Renyi A. (1966) In vivo inhibition of 3H-noradrenaline uptake by mouse brain slices in vitro. J. Pharm. Pharmacol. 18, 322–323.PubMedCrossRefGoogle Scholar
  15. Sakurada S. (1975) Central action ofβ-phenylethylamine derivatives (6) Head-twitches induced by intracerebrally administered tyramine in isocarboxazide pretreated mice. Folia. Pharmacol. Japon 71, 779–787.CrossRefGoogle Scholar
  16. Teresa M., Silva A. and Calil H.M. (1975) Screenig hallucinogenic drugs: Systematic study of three behavioral tests. Psychopharmacol. 42, 163–171.CrossRefGoogle Scholar

Copyright information

© The Human Press Inc. 1985

Authors and Affiliations

  • Kensuke Kisara
    • 1
  • Takeshi Tadano
    • 1
  • Shinetsu Satoh
    • 1
  • Hiroyasu Kinemuchi
    • 2
  1. 1.Department of PharmacologyTohoku College of PharmacySendaiJapan
  2. 2.Department of Pharmacology, School of MedicineShowa UniversityTokyoJapan

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