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

• DOI: 10.7554/elife.09275
• Publication Date: 2015-07-24T11:35:44Z
• Authors: Ming Chen; Yanfang Zhao; Hualan Yang; Wenjie Luan; Jiaojiao Song; Dongyang Cui; Yi Dong; Bin Lai; Lan Ma; Ping Zheng
• Keywords: Male; Narcotics; 0301 basic medicine; QH301-705.5; Science; ventral tegmental area; Presynaptic Terminals; dopamine neuron; Glutamic Acid; Rats, Sprague-Dawley; 03 medical and health sciences; glutamate release; Animals; Biology (General); 0303 health sciences; Morphine; Dopaminergic Neurons; Q; Ventral Tegmental Area; R; morphine; GABA neuron; 3. Good health; Medicine; GABAB receptor; Neuroscience

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.