BDNF interacts with endocannabinoids to regulate cocaine-induced synaptic plasticity in mouse midbrain dopamine neurons

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Peng ZhongQing-song Liu

Abstract

Brain-derived neurotrophic factor (BDNF) and endocannabinoids (eCBs) have been individually implicated in behavioral effects of cocaine. The present study examined how BDNF-eCB interaction regulates cocaine-induced synaptic plasticity in the ventral tegmental area and behavioral effects. We report that BDNF and selective tyrosine kinase receptor B (TrkB) agonist 7,8-dihydroxyflavone (DHF) activated the TrkB receptor to facilitate two forms of eCB-mediated synaptic depression, depolarization-induced suppression of inhibition (DSI), and long-term depression (I-LTD) of IPSCs in ventral tegmental area dopamine neurons in mouse midbrain slices. The facilitation appears to be mediated by an increase in eCB production via phospholipase Cγ pathway, but not by an increase in CB1 receptor responsiveness or a decrease in eCB hydrolysis. Using Cre-loxP technology to specifically delete BDNF in dopamine neurons, we showed that eCB-mediated I-LTD, cocaine-induced reduction of GABAergic inhibition, and potentiation of glutamatergic excitation remained intact in wild-type control mice, but were impaired in BDNF conditional knock-out mice. We also showed that cocaine-induced conditioned place preference was attenuated in BDNF conditional knock-...Continue Reading

Citations

Oct 31, 2015·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Ozge Gunduz-CinarAndrew Holmes
Jul 23, 2019·Cerebral Cortex·Giuseppe GangarossaLaurent Venance
Jul 2, 2020·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Zhaohong QinHsiao-Huei Chen
May 13, 2017·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Xiaojie LiuQing-Song Liu
Dec 14, 2018·Frontiers in Cellular Neuroscience·Filipa Fiel FerreiraSara Xapelli
Feb 28, 2019·PeerJ·Cassiano R A F DinizPlinio C Casarotto
Aug 28, 2020·Frontiers in Molecular Neuroscience·Charlotte PietteLaurent Venance
Nov 5, 2020·Revista brasileira de psiquiatria : orgão oficial da Associação Brasileira de Psiquiatria, Asociación Psiquiátrica de la América Latina·Carolina de Meneses-GayaAcioly L Lacerda
Aug 4, 2021·Neuropharmacology·Bryony Laura Winters, Christopher Walter Vaughan

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