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Interpreting DTBZ binding data in rodent: Inherent variability and compensation.

Miguel Mejias1, Jing Yu1,2, Scott Mackey1,3

  • 1Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

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|January 11, 2016
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Summary

Animal source significantly impacts adult rat dopaminergic systems. Unilateral lesion models show compensatory changes, suggesting the unlesioned side is not a suitable control.

Keywords:
6-OHDAVMAT2compensatory changesdopaminelactacystinstriatum

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Radiochemistry

Background:

  • Dopaminergic function is crucial for motor control and is often studied using animal models.
  • Vesicular monoamine transporter type 2 (VMAT2) is a key marker for dopaminergic neuron integrity.
  • [11C]-dihydrotetrabenazine (DTBZ) PET imaging offers a non-invasive method to quantify VMAT2 availability.

Purpose of the Study:

  • To investigate the influence of animal source on baseline dopaminergic function in rats.
  • To evaluate compensatory changes in dopaminergic function following unilateral nigro-striatal pathway lesions.
  • To assess the suitability of the unlesioned hemisphere as a control in unilateral lesion studies.

Main Methods:

  • Positron Emission Tomography (PET) using [11C]-dihydrotetrabenazine (DTBZ) was employed.
  • Adult Sprague-Dawley rats from two distinct sources (Charles River Laboratories and UBC Animal Care Centre) were used.
  • Unilateral lesions of the nigro-striatal pathway were induced.

Main Results:

  • Significant baseline differences in striatal binding potential (BP(ND)) were observed between rats from different sources.
  • DTBZ BP(ND) increased in the striatum contralateral to the lesion after intervention, indicating compensatory mechanisms.
  • The origin of animals influences the development of the adult dopaminergic system.

Conclusions:

  • Animal source is a critical factor affecting the dopaminergic system and should be controlled in research.
  • The unlesioned hemisphere in unilateral lesion models may not serve as an appropriate internal control.
  • Findings have implications for the design and interpretation of studies involving dopaminergic function and lesion models.