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

Chen M, Zhao Y, Yang H, Luan W, Song J, Cui D, Dong Y, Lai B, Ma L, Zheng P - Elife (2015)

Bottom Line: However, it is not known whether morphine has an additional strengthening effect on excitatory input.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Influence of selective presynaptic GABAB receptor antagonist CGP36216 on the effect of morphine on the firing in VTA-DA neurons of mice.(A) Representative spontaneous firing traces recorded before and after morphine (10 μM) in the presence of CGP36216 (100 μM). (B) Time course of spontaneous firing before and after morphine in the presence of CGP36216 (100 μM) (n = 6). (C) Average frequency of spontaneous firing before and after morphine (10 μM) in the presence of CGP36216 (100 μM) (n = 6, P > 0.05, compared to CGP36216 before morphine).DOI:http://dx.doi.org/10.7554/eLife.09275.019
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fig15: Influence of selective presynaptic GABAB receptor antagonist CGP36216 on the effect of morphine on the firing in VTA-DA neurons of mice.(A) Representative spontaneous firing traces recorded before and after morphine (10 μM) in the presence of CGP36216 (100 μM). (B) Time course of spontaneous firing before and after morphine in the presence of CGP36216 (100 μM) (n = 6). (C) Average frequency of spontaneous firing before and after morphine (10 μM) in the presence of CGP36216 (100 μM) (n = 6, P > 0.05, compared to CGP36216 before morphine).DOI:http://dx.doi.org/10.7554/eLife.09275.019

Mentions: As shown in raw firing traces (Author response image 3A) and time course of VTA-DA neuron firing (Author response image 3B), the presence of CGP36216 (100 µM) led to the disappearance of the effect of morphine (10 µM) on VTA-DA neuron firing. The average firing frequency of VTA-DA neurons was 2.2 ± 0.3 Hz before and 2.3 ± 0.2 Hz during 10-15 min after morphine in the presence of CGP36216 (n = 6, paired t test, P > 0.05, compared to CGP36216 before morphine, Author response image 3C).10.7554/eLife.09275.019Author response image 3.Influence of selective presynaptic GABAB receptor antagonist CGP36216 on the effect of morphine on the firing in VTA-DA neurons of mice.


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

Chen M, Zhao Y, Yang H, Luan W, Song J, Cui D, Dong Y, Lai B, Ma L, Zheng P - Elife (2015)

Influence of selective presynaptic GABAB receptor antagonist CGP36216 on the effect of morphine on the firing in VTA-DA neurons of mice.(A) Representative spontaneous firing traces recorded before and after morphine (10 μM) in the presence of CGP36216 (100 μM). (B) Time course of spontaneous firing before and after morphine in the presence of CGP36216 (100 μM) (n = 6). (C) Average frequency of spontaneous firing before and after morphine (10 μM) in the presence of CGP36216 (100 μM) (n = 6, P > 0.05, compared to CGP36216 before morphine).DOI:http://dx.doi.org/10.7554/eLife.09275.019
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4538365&req=5

fig15: Influence of selective presynaptic GABAB receptor antagonist CGP36216 on the effect of morphine on the firing in VTA-DA neurons of mice.(A) Representative spontaneous firing traces recorded before and after morphine (10 μM) in the presence of CGP36216 (100 μM). (B) Time course of spontaneous firing before and after morphine in the presence of CGP36216 (100 μM) (n = 6). (C) Average frequency of spontaneous firing before and after morphine (10 μM) in the presence of CGP36216 (100 μM) (n = 6, P > 0.05, compared to CGP36216 before morphine).DOI:http://dx.doi.org/10.7554/eLife.09275.019
Mentions: As shown in raw firing traces (Author response image 3A) and time course of VTA-DA neuron firing (Author response image 3B), the presence of CGP36216 (100 µM) led to the disappearance of the effect of morphine (10 µM) on VTA-DA neuron firing. The average firing frequency of VTA-DA neurons was 2.2 ± 0.3 Hz before and 2.3 ± 0.2 Hz during 10-15 min after morphine in the presence of CGP36216 (n = 6, paired t test, P > 0.05, compared to CGP36216 before morphine, Author response image 3C).10.7554/eLife.09275.019Author response image 3.Influence of selective presynaptic GABAB receptor antagonist CGP36216 on the effect of morphine on the firing in VTA-DA neurons of mice.

Bottom Line: However, it is not known whether morphine has an additional strengthening effect on excitatory input.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus