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

eLife

Dongyang Cui¹  Lan Ma¹  Jiaojiao Song¹  Hualan Yang¹  Yi Dong¹  Ping Zheng¹  Wenjie Luan¹  Ming Chen¹  Yanfang Zhao¹  Bin Lai¹ 

[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;

关键词: dopamine neuron;    GABA neuron;    GABAB receptor;    glutamate release;    morphine;    ventral tegmental area;   

DOI  :  10.7554/eLife.09275

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown