Serotonergic treatment normalizes midbrain dopaminergic neuron increase after periaqueductal gray stimulation
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ORIGINAL ARTICLE
Serotonergic treatment normalizes midbrain dopaminergic neuron increase after periaqueductal gray stimulation Shawn Zheng Kai Tan1 · Yasin Temel2 · Ariel Yovela Chan1 · Andrea Tsz Ching Mok1 · Jose Angelo Udal Perucho3 · Arjan Blokland4 · Luca Aquili5 · Wei Ling Lim1,6 · Lee Wei Lim1,6 Received: 27 September 2019 / Accepted: 15 June 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 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. Keywords Deep brain stimulation · Periaqueductal gray · Fear-like behaviour · Dopamine · Serotonergic system
Introduction The dorsolateral periaqueductal gray (dlPAG) plays a major role fear; it is thought to suppress the facilitatory effects of amygdala activation (Walker and Davis 1997), thereby Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00429-020-02102-w) contains supplementary material, which is available to authorized users. * Wei Ling Lim [email protected] * Lee Wei Lim [email protected] 1
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Neuromodulation Laboratory, School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, People’s Republic of China Departments of Neuroscience and Neurosurgery, Maastricht University, Maastricht, The Netherlands
inhibiting fear expression. Indeed, lesions of the dlPAG has been shown to enhance both unconditional freezing and cue
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