Brain-derived neurotrophic factor-mediated projection-specific regulation of depressive-like and nociceptive behaviors in the mesolimbic reward circuitry

Pain
Di LiuJun-Li Cao

Abstract

Increasing evidence suggests that the mesolimbic reward system plays critical roles in the regulation of depression and nociception; however, its circuitry and cellular mechanisms remain unclear. In this study, we investigated the output-specific regulatory roles of dopaminergic (DA) neurons within the ventral tegmental area (VTA) in depressive-like and nociceptive behaviors in mice subjected to unpredictable chronic mild stress (CMS), using the projection-specific electrophysiological recording, pharmacological manipulation, behavioral test, and molecular biology technologies. We demonstrated that CMS decreased the firing activity in VTA projecting to medial prefrontal cortex (VTA → mPFC), but not in VTA to nucleus accumbens (VTA → NAc), DA neurons. However, both VTA → mPFC and VTA → NAc DA neurons showed increased firing activity in response to morphine perfusion in CMS mice. Behavioral results showed that intra-VTA microinjection of morphine (25.5 ng/0.15 μL) relieved depressive-like behaviors, intriguingly, accompanied by a thermal hyperalgesia. Furthermore, the relief of depressive-like behaviors induced by intra-VTA injection of morphine in CMS mice could be prevented by blocking brain-derived neurotrophic factor (BDNF) s...Continue Reading

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Citations

Feb 20, 2019·Cell and Tissue Research·Muris HumoIpek Yalcin
Sep 14, 2019·The International Journal of Neuroscience·Yiling QianYanqiang Li
Aug 30, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Li MaJiu-Hong Kang
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May 20, 2020·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Di LiuJun-Li Cao
Dec 2, 2020·Progress in Lipid Research·Hiroshi Ueda
Nov 19, 2019·Behavioural Brain Research·Millie Rincón-Cortés, Anthony A Grace
Jun 9, 2021·The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry·Gabriele Cheiran PereiraGuilherme Vargas Bochi

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