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Serotonergic treatment normalizes midbrain dopaminergic neuron increase after periaqueductal gray stimulation.
Brain Struct Funct. 2020 Jun 27 [Online ahead of print]BS

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.

Authors+Show Affiliations

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.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.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.Department of Diagnostic Radiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.Department of Neuropsychology and Psychopharmacology, Maastricht University, Maastricht, The Netherlands.School of Psychological and Clinical Sciences, Charles Darwin University, Darwin, Australia.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. weilingl@sunway.edu.my. Department of Biological Sciences, School of Science and Technology, Sunway University, Bandar Sunway, Selangor, Malaysia. weilingl@sunway.edu.my.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. drlimleewei@gmail.com. Department of Biological Sciences, School of Science and Technology, Sunway University, Bandar Sunway, Selangor, Malaysia. drlimleewei@gmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32594260

Citation

Tan, Shawn Zheng Kai, et al. "Serotonergic Treatment Normalizes Midbrain Dopaminergic Neuron Increase After Periaqueductal Gray Stimulation." Brain Structure & Function, 2020.
Tan SZK, Temel Y, Chan AY, et al. Serotonergic treatment normalizes midbrain dopaminergic neuron increase after periaqueductal gray stimulation. Brain Struct Funct. 2020.
Tan, S. Z. K., Temel, Y., Chan, A. Y., Mok, A. T. C., Perucho, J. A. U., Blokland, A., Aquili, L., Lim, W. L., & Lim, L. W. (2020). Serotonergic treatment normalizes midbrain dopaminergic neuron increase after periaqueductal gray stimulation. Brain Structure & Function. https://doi.org/10.1007/s00429-020-02102-w
Tan SZK, et al. Serotonergic Treatment Normalizes Midbrain Dopaminergic Neuron Increase After Periaqueductal Gray Stimulation. Brain Struct Funct. 2020 Jun 27; PubMed PMID: 32594260.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Serotonergic treatment normalizes midbrain dopaminergic neuron increase after periaqueductal gray stimulation. AU - Tan,Shawn Zheng Kai, AU - Temel,Yasin, AU - Chan,Ariel Yovela, AU - Mok,Andrea Tsz Ching, AU - Perucho,Jose Angelo Udal, AU - Blokland,Arjan, AU - Aquili,Luca, AU - Lim,Wei Ling, AU - Lim,Lee Wei, Y1 - 2020/06/27/ PY - 2019/09/27/received PY - 2020/06/15/accepted PY - 2020/6/29/entrez KW - Deep brain stimulation KW - Dopamine KW - Fear-like behaviour KW - Periaqueductal gray KW - Serotonergic system JF - Brain structure & function JO - Brain Struct Funct N2 - 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. SN - 1863-2661 UR - https://www.unboundmedicine.com/medline/citation/32594260/Serotonergic_treatment_normalizes_midbrain_dopaminergic_neuron_increase_after_periaqueductal_gray_stimulation L2 - https://dx.doi.org/10.1007/s00429-020-02102-w DB - PRIME DP - Unbound Medicine ER -
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