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

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
DOI: 10.7554/elife.09275 Publication Date: 2015-07-24T11:35:44Z
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.
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