2. Academic Validation
  3. Morphine disinhibits glutamatergic input to VTA dopamine neurons and promotes dopamine neuron excitation

Morphine disinhibits glutamatergic input to VTA dopamine neurons and promotes dopamine neuron excitation

  • Elife. 2015 Jul 24:4:e09275. doi: 10.7554/eLife.09275.
Ming Chen 1,  Yanfang Zhao 1,  Hualan Yang 1,  Wenjie Luan 1,  Jiaojiao Song 1,  Dongyang Cui 1,  Yi Dong 1,  Bin Lai 1,  Lan Ma 1,  Ping Zheng 1
Affiliations

Affiliation

  • 1 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.
PMID: 26208338 DOI: 10.7554/eLife.09275
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.

Keywords

GABA neurons; GABAB receptors; dopamine neurons; glutamate release; morphine; mouse; neuroscience; rat; ventral tegmental area.

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