Hypoxia-Associated Changes in Striatal Tonic Dopamine Release: Real-Time in vivo Measurements With a Novel Voltammetry Technique.

Abhijeet S Barath,Kendall H Lee,Juan M Rojas Cabrera,Aaron E Rusheen,Hojin Shin,Yoonbae Oh,Robert L Owen,J Blair Price,Dong Pyo Jang,Charles D Blaha

doi:10.3389/fnins.2020.00869

Abhijeet S Barath, Kendall H Lee + Show 8 more

Open Access

https://doi.org/10.3389/fnins.2020.00869

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Abstract

Introduction Striatal tonic dopamine increases rapidly during global cerebral hypoxia. This phenomenon has previously been studied using microdialysis techniques which have relatively poor spatio-temporal resolution. In this study, we measured changes in tonic dopamine during hypoxia (death) in real time with high spatio-temporal resolution using novel multiple cyclic square wave voltammetry (MCSWV) and conventional fast scan cyclic voltammetry (FSCV) techniques.MethodsMCSWV and FSCV were used to measure dopamine release at baseline and during hypoxia induced by euthanasia, with and without prior alpha-methyl-p-tyrosine (AMPT) treatment, in urethane anesthetized male Sprague-Dawley rats.ResultsBaseline tonic dopamine levels were found to be 274.1 ± 49.4 nM (n = 5; mean ± SEM). Following intracardiac urethane injection, the tonic levels increased to a peak concentration of 1753.8 ± 95.7 nM within 3.6 ± 0.6 min (n = 5), followed by a decline to 50.7 ± 21.5 nM (n = 4) at 20 min. AMPT pre-treatment significantly reduced this dopamine peak to 677.9 ± 185.7 nM (n = 3). FSCV showed a significantly higher (p = 0.0079) peak dopamine release of 6430.4 ± 1805.7 nM (n = 5) during euthanasia-induced cerebral hypoxia.ConclusionMCSWV is a novel tool to study rapid changes in tonic dopamine release in vivo during hypoxia. We found a 6-fold increase in peak dopamine levels during hypoxia which was attenuated with AMPT pre-treatment. These changes are much lower compared to those found with microdialysis. This could be due to improved estimation of baseline tonic dopamine with MCSWV. Higher dopamine response measured with FSCV could be due to an increased oxidation current from electroactive interferents.

Highlights

Striatal tonic dopamine increases rapidly during global cerebral hypoxia
We have shown that the massive dopamine release occurring with euthanasia-induced global cerebral hypoxia can be quantified in real time with high spatial (≈50 μm) and temporal resolution (≈10 s) using multiple cyclic square wave voltammetry (MCSWV)
It has been proposed that a trauma layer surrounding the microdialysis probe suppresses dopamine release and that reuptake removes much of the dopamine diffusing toward the probe leading to an underestimation of tonic extracellular concentrations (Chefer et al, 2009)

Summary

Introduction

Striatal tonic dopamine increases rapidly during global cerebral hypoxia This phenomenon has previously been studied using microdialysis techniques which have relatively poor spatio-temporal resolution. The hypoxia sensory neurons, glomus type I cells of the carotid body, release dopamine and other neurotransmitters in response to hypoxia (Toledo-Aral et al, 2002; Carroll and Kim, 2005). Another interesting observation is a blunted response to hypoxia and impaired perception of dyspnea in patients with Parkinson’s disease and individuals who have had bilateral carotid body removal (Lugliani et al, 1971; Onodera et al, 2000). These observations suggest an intimate relationship between hypoxia and dopaminergic neurons

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