BDNF interacts with endocannabinoids to regulate cocaine-induced synaptic plasticity in mouse midbrain dopamine neurons. J Neurosci 2015 Mar 11;35(10):4469-81
Date
03/13/2015Pubmed ID
25762688Pubmed Central ID
PMC4355208DOI
10.1523/JNEUROSCI.2924-14.2015Scopus ID
2-s2.0-84924463268 (requires institutional sign-in at Scopus site) 33 CitationsAbstract
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-out mice, in vivo pretreatments with DHF before place conditioning restored cocaine conditioned place preference in these mice, and the behavioral effect of DHF was blocked by a CB₁ receptor antagonist. Together, these results suggest that BDNF in dopamine neurons regulates eCB responses, cocaine-induced synaptic plasticity, and associative learning.
Author List
Zhong P, Liu Y, Hu Y, Wang T, Zhao YP, Liu QSAuthor
Qing-song Liu PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBrain-Derived Neurotrophic Factor
Carbazoles
Cocaine
Conditioning, Operant
Dopamine Plasma Membrane Transport Proteins
Dopamine Uptake Inhibitors
Dopaminergic Neurons
Endocannabinoids
Enzyme Inhibitors
In Vitro Techniques
Indole Alkaloids
Mesencephalon
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neuronal Plasticity
Piperidines
Pyrazoles
RNA, Untranslated
Receptors, Glutamate
Signal Transduction
Synapses
Time Factors
