The vesicular monoamine transporter (VMAT-2) inhibitor tetrabenazine induces tremulous jaw movements in rodents: Implications for pharmacological models of parkinsonian tremor

S. J. Podurgiel, E. J. Nunes, S. E. Yohn, J. Barber, A. Thompson, M. Milligan, C. A. Lee, L. López-Cruz, M. Pardo, O. Valverde, C. Lendent, Y. Baqi, C. E. Müller, M. Correa, J. D. Salamone

Research output: Contribution to journalArticle

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Abstract

Tetrabenazine (TBZ) is a reversible inhibitor of vesicular monoamine storage that is used to treat Huntington's disease. TBZ preferentially depletes striatal dopamine (DA), and patients being treated with TBZ often experience parkinsonian side effects. The present studies were conducted to investigate the ability of TBZ to induce tremulous jaw movements (TJMs), which are a rodent model of parkinsonian tremor, and to determine if interference with adenosine A2A receptor transmission can attenuate TJMs and other motor effects of TBZ. In rats, TBZ (0.25-2.0mg/kg) significantly induced TJMs, which primarily occurred in the 3.0-7.5-Hz frequency range. The adenosine A2A antagonist MSX-3 (1.25-10.0mg/kg) significantly attenuated the TJMs induced by 2.0mg/kg TBZ in rats, and also significantly reduced the display of catalepsy and locomotor suppression induced by TBZ. In mice, TBZ (2.5-10.0mg/kg) dose dependently induced TJMs, and adenosine A2A receptor knockout mice showed significantly fewer TJMs compared to wild-type controls. MSX-3 (2.5-10.0mg/kg) also significantly reduced TBZ-induced TJMs in CD1 mice. To provide a cellular marker of these pharmacological conditions, we examined c-Fos expression in the ventrolateral neostriatum (VLS). TBZ (2.0mg/kg) significantly increased the number of c-Fos-positive cells in the VLS, which is indicative of reduced DA D2 receptor transmission, and 10.0mg/kg MSX-3 significantly attenuated the TBZ-induced c-Fos expression. These results indicate that TBZ induces tremor as measured by the TJM model, and that pharmacological antagonism and genetic deletion of adenosine A2A receptors are capable of attenuating this oral tremor.

Original languageEnglish
Pages (from-to)507-519
Number of pages13
JournalNeuroscience
Volume250
DOIs
Publication statusPublished - Oct 2013

Fingerprint

Tetrabenazine
Vesicular Monoamine Transport Proteins
Tremor
Jaw
Rodentia
Pharmacology
Adenosine A2A Receptors
Neostriatum
Catalepsy
Corpus Striatum
Aptitude
Dopamine D2 Receptors
Huntington Disease

Keywords

  • Adenosine
  • C-Fos
  • Dopamine
  • Huntington's
  • Parkinson's
  • Tremor

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

The vesicular monoamine transporter (VMAT-2) inhibitor tetrabenazine induces tremulous jaw movements in rodents : Implications for pharmacological models of parkinsonian tremor. / Podurgiel, S. J.; Nunes, E. J.; Yohn, S. E.; Barber, J.; Thompson, A.; Milligan, M.; Lee, C. A.; López-Cruz, L.; Pardo, M.; Valverde, O.; Lendent, C.; Baqi, Y.; Müller, C. E.; Correa, M.; Salamone, J. D.

In: Neuroscience, Vol. 250, 10.2013, p. 507-519.

Research output: Contribution to journalArticle

Podurgiel, SJ, Nunes, EJ, Yohn, SE, Barber, J, Thompson, A, Milligan, M, Lee, CA, López-Cruz, L, Pardo, M, Valverde, O, Lendent, C, Baqi, Y, Müller, CE, Correa, M & Salamone, JD 2013, 'The vesicular monoamine transporter (VMAT-2) inhibitor tetrabenazine induces tremulous jaw movements in rodents: Implications for pharmacological models of parkinsonian tremor', Neuroscience, vol. 250, pp. 507-519. https://doi.org/10.1016/j.neuroscience.2013.07.008
Podurgiel, S. J. ; Nunes, E. J. ; Yohn, S. E. ; Barber, J. ; Thompson, A. ; Milligan, M. ; Lee, C. A. ; López-Cruz, L. ; Pardo, M. ; Valverde, O. ; Lendent, C. ; Baqi, Y. ; Müller, C. E. ; Correa, M. ; Salamone, J. D. / The vesicular monoamine transporter (VMAT-2) inhibitor tetrabenazine induces tremulous jaw movements in rodents : Implications for pharmacological models of parkinsonian tremor. In: Neuroscience. 2013 ; Vol. 250. pp. 507-519.
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