Skip to main content
SpringerLink
Log in

Increased sensitivity of mice to tremorogenic agents following MPP+

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

The behavioral effects following intrastriatal MPP+, the neurotoxic metabolite of MPTP, were evaluated in mice. Bilateral injections of 10 ίcro;g MPP+ to mice previously trained in the shuttle box paradigm produced a 66% decrease in striatal dopamine and significant deficits in all measures of conditioned avoidance responding. In addition, although these mice showed no deficits in baseline rotorod performance, challenge with the cholinergic agonist oxotremorine revealed that MPP+-treated mice exhibited an increased sensitivity to the disruptive effects of the drug at each dose and time point. Finally, MPP+-treated mice also exhibited an increase in tremor induced by 0.1 and 0.15 mg/kg oxotremorine. These observations are discussed in reference to idiopathic parkinsonism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Ballard P, Tetrud J, Langston JW (1985) Permanent human parkinsonism due to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-Seven cases. Neurology 35:949–956

    Google Scholar 

  • Burns RS, Chiueh C, Markey S, Ebert M, Jacobowitz D, Kopin I (1983) A primate model of parkinsonism: Selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by n-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proc Natl Acad Sci USA 80:4546–4550

    Google Scholar 

  • Chiba K, Trevor A, Castagnoli N (1984) Metabolism of the neurotoxic tertiary amine, MPTP, by brain monoamine oxidase. Biochem Biophys Res Commun 120 (2):574–578

    Google Scholar 

  • Chiueh CC, Markey SP, Burns RS, Johannessen JN, Jacobowitz D, Kopin I (1983) I-N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a parkinsonian syndrome causing agent in man and monkey, produces different effects in guinea pig and rat. The Pharmacologist 25:131

    Google Scholar 

  • Davis G, Williams A, Markey S, Ebert M, Caine E, Reichert C, Kopin I (1979) Chronic parkinsonism secondary to intravenous injection of meperidine analogues. Psychiatr Res 1:249–254

    Google Scholar 

  • Duvoisin R (1967) Cholinergic-anticholinergic antagonism in parkinsonism. Arch Neurol 17:124–136

    Google Scholar 

  • Heikkila R, Hess A, Duvoisin R (1984) Dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine in mice. Science 224:1451–1453

    Google Scholar 

  • Izumi K, Nomoto M, Koja T, Shimuzu T, Kishita C, Fukuda T (1984) Phenytoin potentiates methamphetamine induced behavior in mice. Pharmacol Biochem Behav 20:803–806

    Google Scholar 

  • Jarvis MF, Wagner GC (1985) Neurochemical and functional consequences following 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) and methamphetamine. Life Sci 36:249–254

    Google Scholar 

  • Lang AE (1984) Treatment of Parkinson's disease with agents other than levodopa and dopamine agonists: Controversies and new approaches. Can J Neurol Sci 11:210–220

    Google Scholar 

  • Langston JW (1985) MPTP Neurotoxicity: An overview and characterization of phases of toxicity. Life Sci 36:201–206

    Google Scholar 

  • Langston JW, Ballard P, Tetrud JW, Irwin I (1983) Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219:979–980

    CAS  PubMed  Google Scholar 

  • Lenard LG, Beer B (1975) Relationship of brain levels of norepinephrine and dopamine to avoidance behavior in rats after intraventricular administration of 6-hydroxydopamine. Pharmacol Biochem Behav 3:895–899

    Google Scholar 

  • Lloyd KG, Davidson L, Hornykiewicz O (1975) The neurochemistry of Parkinson's disease: Effect of L-dopa. J Pharmacol Exp Ther 195:453–464

    Google Scholar 

  • Neill DB, Boggan WO, Grossman SP (1974) Impairment of avoidance performance by intrastriatal administration of 6-hydroxydopamine. Pharmacol Biochem Behav 2:97–103

    Google Scholar 

  • Seiden LS, Carlsson A (1963) Temporary and partial antagonism by L-dopa of reserpine induced suppression of a conditioned avoidance response. Psychopharmacologia 4:418–423

    Google Scholar 

  • Wagner GC, Gardener I, Tsigas DJ, Masters DB (1984) Tolerance following the repeated administration of phencyclidine: No relation to central catecholamine depletion. Drug Alcohol Depend 13:225–234

    Google Scholar 

  • Wagner GC, Jarvis MF, Rubin JG (1986) L-Dopa reverses the effects of MPP+ toxicity. Psychopharmacology 88:401–402

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychology, Rutgers, The State University, 08903, New Brunswick, NJ, USA

    G. C. Wagner & S. L. Walsh

Authors
  1. G. C. Wagner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. L. Walsh
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wagner, G.C., Walsh, S.L. Increased sensitivity of mice to tremorogenic agents following MPP+ . Psychopharmacology 92, 470–472 (1987). https://doi.org/10.1007/BF00176480

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00176480

Key words

Search

Navigation