title: Morphine disinhibits glutamatergic input to VTA dopamine neurons and promotes dopamine neuron excitation.
abstract: One reported mechanism for morphine activation of dopamine (DA) neurons of the ventral tegmental area (VTA) is the disinhibition model of VTA-DA neurons. Morphine inhibits GABA inhibitory neurons, which shifts the balance between inhibitory and excitatory input to VTA-DA neurons in favor of excitation and then leads to VTA-DA neuron excitation. However, it is not known whether morphine has an additional strengthening effect on excitatory input. Our results suggest that glutamatergic input to VTA-DA neurons is inhibited by GABAergic interneurons via GABAB receptors and that morphine promotes presynaptic glutamate release by removing this inhibition. We also studied the contribution of the morphine-induced disinhibitory effect on the presynaptic glutamate release to the overall excitatory effect of morphine on VTA-DA neurons and related behavior. Our results suggest that the disinhibitory action of morphine on presynaptic glutamate release might be the main mechanism for morphine-induced increase in VTA-DA neuron firing and related behaviors.
authors.affiliation: State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan Univeristy, Shanghai, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan Univeristy, Shanghai, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan Univeristy, Shanghai, China.
authors.forename: Hualan
authors.initials: H
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan Univeristy, Shanghai, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Luan
authors.affiliation: State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan Univeristy, Shanghai, China.
authors.forename: Jiaojiao
authors.initials: J
authors.lastname: Song
authors.affiliation: State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan Univeristy, Shanghai, China.
authors.forename: Dongyang
authors.initials: D
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan Univeristy, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan Univeristy, Shanghai, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Lai
authors.affiliation: State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan Univeristy, Shanghai, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan Univeristy, Shanghai, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zheng
mesh_terms: D000818:Animals; D059290:Dopaminergic Neurons / Q000187:drug effects*; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000378:metabolism*; D009294:Narcotics / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D017557:Ventral Tegmental Area / Q000187:drug effects*
chemical_list: D009294:Narcotics; D018698:Glutamic Acid; D009020:Morphine
keywords: GABA neurons; GABAB receptors; dopamine neurons; glutamate release; morphine; mouse; neuroscience; rat; ventral tegmental area