Neurodegeneration, Neuroprotection, and Disease-Oriented NeuroscienceResearch PaperEffects of noradrenaline and serotonin depletions on the neuronal activity of globus pallidus and substantia nigra pars reticulata in experimental parkinsonism
Highlights
▶5-HT depletion induces dramatic changes in the firing activity of GP and SNr neurons. ▶Noradrenaline or 5-HT depletion did not potentiate the changes induced by DA depletion. ▶Noradrenaline and 5-HT depletion contribute to the dysregulation of the basal ganglia.
Section snippets
Animals
Adult male Sprague–Dawley rats, weighing 280–380 g were used. They were housed five per cage under artificial conditions of light (light/dark cycle, light on at 7:00 am), temperature (24 °C), and humidity (45%) with food and water available ad libitum. All animal experiments were carried out in accordance with European Communities Council Directive 2010/63/UE, and all efforts were made to minimize the number of animals used and their suffering.
Drugs
6-OHDA, DSP-4, pCPA, ascorbic acid, desipramine
Effect of 6-OHDA, DSP-4, and pCPA on monoamine tissue concentrations in the rat brain
Table 1 summarizes the tissue concentration values of DA in the anterior striatum and NA and 5-HT in the frontal cortex in the six experimental groups (see Fig. 1). The 6-OHDA, DSP-4, and pCPA administrations applied alone or combined (6-OHDA/DSP-4 and 6-OHDA/pCPA) induced a selective depletion of endogenous DA, NA, and 5-HT, respectively, without modifying other monoamines.
Discussion
The present study shows that additional depletion of NA or 5-HT to dopamine depletion influences in a region-dependent manner the electrophysiological properties of GP and SNr neurons. Although NA depletion alone did not alter GP and SNr neuronal activity, it dampened the pathological increase in irregular and bursty pallidal neurons induced by the DA depletion. 5-HT depletion alone induced similar effects to the 6-OHDA lesion (except for a decreased firing rate in the GP). The increased bursty
Conclusion
The results of the present study provide evidence that the 5-HT system plays a major role in the modulation of both the firing rate and patterns of GP and SNr neurons. Although the influence of the NA system on these brain regions is weak, it strongly modulates the activity of STN neurons (Delaville et al., in press). These data show that, in addition to the prominent influence of DA neurons on basal ganglia activity, NA and 5-HT neurons also participate in the overall homeostasis of this
Acknowledgments
Claire Delaville was supported by a fellowship from the “Ministère de l'Education Nationale, de la Recherche et de la Technologie” (MENRT). The University Bordeaux Segalen and the “Centre National de la Recherche Scientifique” (CNRS) funded this study. We wish to thank Dr. Martin Guthrie for english reading of the manuscript.
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