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Effects of blocking the dopamine biosynthesis and of neurotoxic dopamine depletion with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on voluntary wheel running in mice.
Behav Brain Res. 2004 Oct 05; 154(2):375-83.BB

Abstract

In Parkinson's disease (PD) compensatory mechanisms such as an increase of the de novo biosynthesis of dopamine (DA) are thought to delay the onset of motor impairment. Here, we investigated whether the tyrosine hydroxylase (TH) inhibitor alpha-methyl-para-tyrosine (AMPT) affects behavioral deficits in the running wheel activity induced by the selective dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Immediately after MPTP treatment C57bl/6 mice showed reduced running wheel activity which lasted during the entire active phase (20:00 to 08:00 h), recovered to baseline levels in the following 2 days and remained stable up to the end of the experiment. AMPT challenge significantly reduced wheel running activity in MPTP-treated mice in the first 3 h after treatment. Post mortem HPLC analysis detected mean striatal DA levels in saline + saline and saline + AMPT-treated mice of 14.32 and 9.83 ng/mg, respectively and in MPTP + saline and MPTP + AMPT-treated mice of 1.73 and 0.69 ng/mg, respectively. Taken together, de novo biosynthesis of DA is a crucial component of the compensatory mechanisms which contributes to masking long-term behavioral deficits in the MPTP mouse model. Additionally, wheel running activity might provide a useful tool to study MPTP-induced behavioral deficits, shifts in circadian rhythmicity, and further compensatory mechanisms relevant to PD.

Authors+Show Affiliations

Laboratory of Behavioural Neurobiology, Swiss Federal Institute of Technology Zurich, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15313025

Citation

Leng, Andreas, et al. "Effects of Blocking the Dopamine Biosynthesis and of Neurotoxic Dopamine Depletion With 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) On Voluntary Wheel Running in Mice." Behavioural Brain Research, vol. 154, no. 2, 2004, pp. 375-83.
Leng A, Mura A, Hengerer B, et al. Effects of blocking the dopamine biosynthesis and of neurotoxic dopamine depletion with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on voluntary wheel running in mice. Behav Brain Res. 2004;154(2):375-83.
Leng, A., Mura, A., Hengerer, B., Feldon, J., & Ferger, B. (2004). Effects of blocking the dopamine biosynthesis and of neurotoxic dopamine depletion with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on voluntary wheel running in mice. Behavioural Brain Research, 154(2), 375-83.
Leng A, et al. Effects of Blocking the Dopamine Biosynthesis and of Neurotoxic Dopamine Depletion With 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) On Voluntary Wheel Running in Mice. Behav Brain Res. 2004 Oct 5;154(2):375-83. PubMed PMID: 15313025.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of blocking the dopamine biosynthesis and of neurotoxic dopamine depletion with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on voluntary wheel running in mice. AU - Leng,Andreas, AU - Mura,Anna, AU - Hengerer,Bastian, AU - Feldon,Joram, AU - Ferger,Boris, PY - 2003/10/14/received PY - 2004/03/04/revised PY - 2004/03/04/accepted PY - 2004/8/18/pubmed PY - 2004/11/2/medline PY - 2004/8/18/entrez SP - 375 EP - 83 JF - Behavioural brain research JO - Behav. Brain Res. VL - 154 IS - 2 N2 - In Parkinson's disease (PD) compensatory mechanisms such as an increase of the de novo biosynthesis of dopamine (DA) are thought to delay the onset of motor impairment. Here, we investigated whether the tyrosine hydroxylase (TH) inhibitor alpha-methyl-para-tyrosine (AMPT) affects behavioral deficits in the running wheel activity induced by the selective dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Immediately after MPTP treatment C57bl/6 mice showed reduced running wheel activity which lasted during the entire active phase (20:00 to 08:00 h), recovered to baseline levels in the following 2 days and remained stable up to the end of the experiment. AMPT challenge significantly reduced wheel running activity in MPTP-treated mice in the first 3 h after treatment. Post mortem HPLC analysis detected mean striatal DA levels in saline + saline and saline + AMPT-treated mice of 14.32 and 9.83 ng/mg, respectively and in MPTP + saline and MPTP + AMPT-treated mice of 1.73 and 0.69 ng/mg, respectively. Taken together, de novo biosynthesis of DA is a crucial component of the compensatory mechanisms which contributes to masking long-term behavioral deficits in the MPTP mouse model. Additionally, wheel running activity might provide a useful tool to study MPTP-induced behavioral deficits, shifts in circadian rhythmicity, and further compensatory mechanisms relevant to PD. SN - 0166-4328 UR - https://www.unboundmedicine.com/medline/citation/15313025/Effects_of_blocking_the_dopamine_biosynthesis_and_of_neurotoxic_dopamine_depletion_with_1_methyl_4_phenyl_1236_tetrahydropyridine__MPTP__on_voluntary_wheel_running_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166432804000841 DB - PRIME DP - Unbound Medicine ER -