Neurochemical Research

, Volume 30, Issue 11, pp 1377–1385 | Cite as

Effects of Monoamine Oxidase Inhibitors on Methamphetamine-Induced Stereotypy in Mice and Rats

  • Tomohiro Tatsuta
  • Nobue Kitanaka
  • Junichi Kitanaka
  • Yoshio Morita
  • Motohiko Takemura


In male ICR mice, a single intraperitoneal administration of methamphetamine (METH) (10 mg/kg) induced stereotyped behavior such as continuous sniffing, circling, and nail biting, reaching a plateau level 20 min after the injection. Subcutaneous pretreatment with clorgyline, a monoamine oxidase (MAO)-A inhibitor, at a dose of 0.1 mg/kg 2 h prior to the drug challenge significantly decreased the initial (first 20 min) intensity of stereotypies and increased the latency to onset. The effect was not observed with either higher doses of clorgyline (1 and 10 mg/kg) or l-deprenyl, a MAO-B inhibitor, at doses of 0.1–10 mg/kg. In male Wistar rats, the inhibitory effect of clorgyline on METH-induced stereotypy was not observed. Pretreatment of the mice with clorgyline (0.1 mg/kg) had no effect on apparent serotonin and dopamine turnover in the striatum, although the higher doses of clorgyline (1 and 10 mg/kg) significantly decreased the turnover. These results suggest that a low dose of clorgyline tends to increase the latency and decrease the intensity of stereotypies induced by METH in a dopamine metabolism-independent manner in mice.


Clorgyline methamphetamine monoamine turnover species difference stereotypy 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Snyder, S. H. 1972Catecholamines in the brain as mediators of amphetamine psychosisArch. Gen. Psychiat.27169179PubMedGoogle Scholar
  2. 2.
    Ellinwood, E. H., Kilbey, M. M. 1977Chronic stimulant intoxication models of psychosisHanin, I.Usdin, E. eds. Animal Models in Psychiatry and NeurologyPergamon PressNew York6174Google Scholar
  3. 3.
    Nishikawa, T., Mataga, N., Takashima, M., Toru, M. 1983Behavioral sensitization and relative hyperresponsiveness of striatal and limbic dopaminergic neurons after repeated methamphetamine treatmentEur. J. Pharmacol.88195203CrossRefPubMedGoogle Scholar
  4. 4.
    Robinson, T. E., Becker, J. B. 1986Enduring changes in brain and behavior produced by chronic amphetamine administration: a review and evaluation of animal models of amphetamine psychosisBrain Res. Rev.11157198CrossRefGoogle Scholar
  5. 5.
    Seiden, L. S., Sabol, K. E., Ricaurte, G. A. 1993Amphetamine: Effects on catecholamine systems and behaviorAnnu. Rev. Pharmacol. Toxicol.32639677Google Scholar
  6. 6.
    Gainetdinov, R. R., Mohn, A. R., Caron, M. G. 2001Genetic animal models: Focus on schizophreniaTrends Neurosci.24527533CrossRefPubMedGoogle Scholar
  7. 7.
    Chipkin, R. E., McQuade, R. D., Iorio, L. C. 1987D1 and D2 dopamine binding site up-regulation and apomorphine-induced stereotypyPharmacol. Biochem. Behav.28477482CrossRefPubMedGoogle Scholar
  8. 8.
    Delfs, J. M., Kelley, A. E. 1990The role of D1 and D2 dopamine receptors in oral stereotypy induced by dopaminergic stimulation of the ventrolateral striatumNeuroscience395967CrossRefPubMedGoogle Scholar
  9. 9.
    Conti, L. H., Segal, D. S., Kuczenski, R. 1997Maintenance of amphetamine-induced stereotypy and locomotion requires ongoing dopamine receptor activationPsychopharmacology (Berl)130183188Google Scholar
  10. 10.
    Kuczenski, R., Segal, D. S 1999Sensitization of amphetamine-induced stereotyped behaviors during the acute responseJ. Pharmacol. Exp. Ther.288699709PubMedGoogle Scholar
  11. 11.
    Chartoff, E. H., Marck, B. T., Matsumoto, A. M., Dorsa, D. M., Palmiter, R. D. 2001Induction of stereotypy in dopamine-deficient mice requires striatal D1 receptor activationProc. Natl. Acad. Sci. USA981045110456CrossRefPubMedGoogle Scholar
  12. 12.
    Murphy, D. L 1978Substrate-selective monoamine oxidases: Inhibitor, tissue, species and functional differencesBiochem. Pharmacol.2718891893PubMedGoogle Scholar
  13. 13.
    Fornai, F., Chen, K., Giorgi, F. S., Gesi, M., Alessandr, M. G., Shih, J. C. 1999Striatal dopamine metabolism in monoamine oxidase B-deficient mice: A brain dialysis studyJ. Neurochem.7324342440CrossRefPubMedGoogle Scholar
  14. 14.
    Institute of Laboratory Animal Resources1996Guide for Care and Use of Laboratory AnimalsNational Academy PressWashington, DCGoogle Scholar
  15. 15.
    Kitanaka, N., Kitanaka, J., Takemura, M. 2003Behavioral sensitization and alteration in monoamine metabolism in mice after single versus repeated methamphetamine administrationEur. J. Pharmacol.4746370CrossRefPubMedGoogle Scholar
  16. 16.
    Kitanaka, N., Kitanaka, J., Takemura, M. 2005Inhibition of methamphetamine-induced hyperlocomotion in mice by clorgyline, a monoamine oxidase-A inhibitor, through alteration of the 5-hydroxytryptamine turnover in the striatumNeuroscience130295308CrossRefPubMedGoogle Scholar
  17. 17.
    Kitanaka, N., Kitanaka, J., Takemura, M. 2005Repeated clorgyline treatment inhibits methamphetamine-induced behavioral sensitization in miceNeurochem. Res.30445451CrossRefPubMedGoogle Scholar
  18. 18.
    Weinshenker, D., Miller, N. S., Blizinsky, K., Laughlin, M. L., Palmiter, R. D. 2002Mice with chronic norepinephrine deficiency resemble amphetamine-sensitized animalsProc. Natl. Acad. Sci. USA211387313877Google Scholar
  19. 19.
    Finberg, J. P., Youdim, M. B. 1983Selective MAO A and B inhibitors: Their mechanism of action and pharmacologyNeuropharmacology22441446CrossRefPubMedGoogle Scholar
  20. 20.
    Felner, A. E., Waldmeier, P. C. 1978Cumulative effects of irreversible MAO inhibitors in vivoBiochem. Pharmacol.289951002Google Scholar
  21. 21.
    Campbell, I. C., Durcan, M. J., Cohen, R. M., Pickar, D., Chugani, D., Murphy, D. L. 1985Chronic clorgyline and pargyline increase apomorphine-induced stereotypy in the ratPharmacol. Biochem. Behav.23921925CrossRefPubMedGoogle Scholar
  22. 22.
    Culver, K. E., Szechtman, H. 1997Monoamine oxidase inhibitor sensitive site implicated in sensitization to quinpiroleEur. J. Pharmacol.339109111CrossRefPubMedGoogle Scholar
  23. 23.
    Culver, K. E., Rosenfeld, J. M., Szechtman, H. 2002Monoamine oxidase inhibitor-induced blockade of locomotor sensitization to quinpirole: Role of striatal dopamine uptake inhibitionNeuropharmacology43285393CrossRefGoogle Scholar
  24. 24.
    Levant, B., Moehlenkamp, J. D., Morgan, K. A., Leonard, N. L., Cheng, C. C. 1996Modulation of [3H]quinpirole binding in brain by monoamine oxidase inhibitors: Evidence for a potential novel binding siteJ. Pharmacol. Exp. Ther.278145153PubMedGoogle Scholar
  25. 25.
    MacInnes, N., Handley, S. L. 2005Autoradiographic localisation of [3H]2-BFI imidazoline I2 binding sites in mouse brainEur. J. Pharmacol.516139144CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Tomohiro Tatsuta
    • 1
    • 2
  • Nobue Kitanaka
    • 1
  • Junichi Kitanaka
    • 1
  • Yoshio Morita
    • 2
  • Motohiko Takemura
    • 1
  1. 1.Department of PharmacologyHyogo College of MedicineNishinomiyaJapan
  2. 2.Department of NeuropsychiatryHyogo College of MedicineNishinomiyaJapan

Personalised recommendations