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01-09-2020 | Deep Brain Stimulation | Original Article

Serotonergic treatment normalizes midbrain dopaminergic neuron increase after periaqueductal gray stimulation

Authors: Shawn Zheng Kai Tan, Yasin Temel, Ariel Yovela Chan, Andrea Tsz Ching Mok, Jose Angelo Udal Perucho, Arjan Blokland, Luca Aquili, Wei Ling Lim, Lee Wei Lim

Published in: Brain Structure and Function | Issue 7/2020

Abstract

Electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) in rats has been shown to elicit panic-like behaviour and can be a useful as an unconditioned stimulus for modelling anticipatory fear and agoraphobia in a contextual fear conditioning paradigm. In this study, we further analysed our previous data on the effects of escitalopram (a selective serotonin reuptake inhibitor, SSRI) and buspirone (a 5-HT1A receptor partial agonist) on dlPAG-induced anticipatory fear behaviour in a rat model using freezing as a measure. We then attempted to unravel some of the interactions with dopamine signalling using tyrosine hydroxylase (TH) immunohistochemistry to probe the effects on dopaminergic neurons. We showed that acute treatment of escitalopram, but not buspirone, was effective in reducing anticipatory freezing behaviour, while chronic administrations of both drugs were effective. We found that the dlPAG stimulation induced increase number of dopaminergic neurons in the ventral tegmental area (VTA) which was reversed in both chronic buspirone and escitalopram groups. We further found a strong positive correlation between the number of dopaminergic neurons and freezing in the VTA and showed positive correlations between dopaminergic neurons in the VTA and substantia nigra pars compacta (SNpc) in escitalopram and buspirone groups, respectively. Overall, we showed that chronic treatment with an SSRI and a 5-HT1A agonist reduced anticipatory freezing behaviour which seems to be associated, through correlative studies, with a reversal of dlPAG stimulation induced increase in number of dopaminergic neurons in the VTA and/or SNpc.

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Title: Serotonergic treatment normalizes midbrain dopaminergic neuron increase after periaqueductal gray stimulation
Authors: Shawn Zheng Kai Tan
Yasin Temel
Ariel Yovela Chan
Andrea Tsz Ching Mok
Jose Angelo Udal Perucho
Arjan Blokland
Luca Aquili
Wei Ling Lim
Lee Wei Lim
Publication date: 01-09-2020
Publisher: Springer Berlin Heidelberg
Keywords: Deep Brain Stimulation
Anxiety
Escitalopram
Published in: Brain Structure and Function / Issue 7/2020
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-020-02102-w

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Serotonergic treatment normalizes midbrain dopaminergic neuron increase after periaqueductal gray stimulation

Abstract

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Abstract

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