PMID- 29076919 OWN - NLM STAT- MEDLINE DCOM- 20190321 LR - 20221005 IS - 1872-6623 (Electronic) IS - 0304-3959 (Print) IS - 0304-3959 (Linking) VI - 159 IP - 1 DP - 2018 Jan TI - Brain-derived neurotrophic factor-mediated projection-specific regulation of depressive-like and nociceptive behaviors in the mesolimbic reward circuitry. PG - 175 LID - 10.1097/j.pain.0000000000001083 [doi] AB - 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 muL) 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) signaling and mimicked by the administration of exogenous BDNF in mPFC rather than in NAc shell. Nociceptive responses induced by the activation of VTA DA neurons with morphine in CMS mice could be prevented by blocking BDNF signaling or mimicked by administration of exogenous BDNF in NAc shell, but not in mPFC. These results reveal projection-specific regulatory mechanisms of depression and nociception in the mesolimbic reward circuitry and provide new insights into the neural circuits involved in the processing of depressive and nociceptive information. FAU - Liu, Di AU - Liu D AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China. AD - Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. FAU - Tang, Qian-Qian AU - Tang QQ AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China. AD - Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. AD - Departments of Emergency ICU and. FAU - Yin, Cui AU - Yin C AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China. AD - Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. FAU - Song, Yu AU - Song Y AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China. AD - Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. FAU - Liu, Yan AU - Liu Y AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China. AD - Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. FAU - Yang, Jun-Xia AU - Yang JX AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China. AD - Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. FAU - Liu, He AU - Liu H AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China. AD - Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. AD - Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, China. FAU - Zhang, Yue-Man AU - Zhang YM AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China. AD - Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. FAU - Wu, Si-Yin AU - Wu SY AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China. AD - Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. FAU - Song, Ying AU - Song Y AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China. AD - Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. FAU - Juarez, Barbara AU - Juarez B AD - Department of Pharmacological Sciences, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. FAU - Ding, Hai-Lei AU - Ding HL AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China. AD - Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. FAU - Han, Ming-Hu AU - Han MH AD - Department of Pharmacological Sciences, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. FAU - Zhang, Hongxing AU - Zhang H AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China. AD - Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. FAU - Cao, Jun-Li AU - Cao JL AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China. AD - Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. AD - Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, China. LA - eng GR - P50 MH096890/MH/NIMH NIH HHS/United States GR - T32 MH087004/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Pain JT - Pain JID - 7508686 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Narcotics) RN - 76I7G6D29C (Morphine) SB - IM MH - Animals MH - Behavior, Animal/*drug effects MH - Brain-Derived Neurotrophic Factor/metabolism/*pharmacology MH - Depression MH - Dopaminergic Neurons/*drug effects/metabolism MH - Male MH - Mice MH - Morphine/pharmacology MH - Narcotics/pharmacology MH - Neural Pathways/drug effects/metabolism MH - Nociception/drug effects MH - Nucleus Accumbens/*drug effects/metabolism MH - Prefrontal Cortex/*drug effects/metabolism MH - Social Behavior MH - Ventral Tegmental Area/*drug effects/metabolism PMC - PMC6764446 MID - NIHMS989525 COIS- The authors declare no conflict of interest. EDAT- 2017/10/28 06:00 MHDA- 2019/03/22 06:00 PMCR- 2019/09/27 CRDT- 2017/10/28 06:00 PHST- 2017/10/28 06:00 [pubmed] PHST- 2019/03/22 06:00 [medline] PHST- 2017/10/28 06:00 [entrez] PHST- 2019/09/27 00:00 [pmc-release] AID - 00006396-201801000-00022 [pii] AID - 10.1097/j.pain.0000000000001083 [doi] PST - ppublish SO - Pain. 2018 Jan;159(1):175. doi: 10.1097/j.pain.0000000000001083.