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Glutamate Transmission to Ventral Tegmental Area GABA Neurons Is Altered by Acute and Chronic Ethanol.
Alcohol Clin Exp Res 2018; 42(11):2186-2195AC

Abstract

BACKGROUND

Ventral tegmental area (VTA) GABA neurons have been heavily implicated in alcohol reinforcement and reward. In animals that self-administer alcohol, VTA GABA neurons exhibit increased excitability that may contribute to alcohol's rewarding effects. The present study investigated the effects of acute and chronic ethanol exposure on glutamate (GLU) synaptic transmission to VTA GABA neurons.

METHODS

Whole-cell recordings of evoked, spontaneous, and miniature excitatory postsynaptic currents (eEPSCs, sEPSCs, and mEPSCs, respectively) were performed on identified GABA neurons in the VTA of GAD67-GFP+ transgenic mice. Three ethanol exposure paradigms were used: acute ethanol superfusion; a single ethanol injection; and chronic vapor exposure.

RESULTS

Acute ethanol superfusion increased the frequency of EPSCs but inhibited mEPSC frequency and amplitude. During withdrawal from a single injection of ethanol, the frequency of sEPSCs was lower than saline controls. There was no difference in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/N-methyl-d-aspartate (NMDA) ratio between neurons following withdrawal from a single exposure to ethanol. However, following withdrawal from chronic ethanol, sEPSCs and mEPSCs had a greater frequency than air controls. There was no difference in AMPA/NMDA ratio following chronic ethanol.

CONCLUSIONS

These results suggest that presynaptic mechanisms involving local circuit GLU neurons, and not GLU receptors, contribute to adaptations in VTA GABA neuron excitability that accrue to ethanol exposure, which may contribute to the rewarding properties of alcohol via their regulation of mesolimbic dopamine transmission.

Authors+Show Affiliations

Department of Psychology and Center for Neuroscience, Brigham Young University, Provo, Utah.Department of Psychology and Center for Neuroscience, Brigham Young University, Provo, Utah.Department of Psychology and Center for Neuroscience, Brigham Young University, Provo, Utah.Department of Psychology and Center for Neuroscience, Brigham Young University, Provo, Utah.Department of Psychology and Center for Neuroscience, Brigham Young University, Provo, Utah.Department of Psychology and Center for Neuroscience, Brigham Young University, Provo, Utah.Department of Psychology and Center for Neuroscience, Brigham Young University, Provo, Utah.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

30204234

Citation

Williams, Stephanie B., et al. "Glutamate Transmission to Ventral Tegmental Area GABA Neurons Is Altered By Acute and Chronic Ethanol." Alcoholism, Clinical and Experimental Research, vol. 42, no. 11, 2018, pp. 2186-2195.
Williams SB, Yorgason JT, Nelson AC, et al. Glutamate Transmission to Ventral Tegmental Area GABA Neurons Is Altered by Acute and Chronic Ethanol. Alcohol Clin Exp Res. 2018;42(11):2186-2195.
Williams, S. B., Yorgason, J. T., Nelson, A. C., Lewis, N., Nufer, T. M., Edwards, J. G., & Steffensen, S. C. (2018). Glutamate Transmission to Ventral Tegmental Area GABA Neurons Is Altered by Acute and Chronic Ethanol. Alcoholism, Clinical and Experimental Research, 42(11), pp. 2186-2195. doi:10.1111/acer.13883.
Williams SB, et al. Glutamate Transmission to Ventral Tegmental Area GABA Neurons Is Altered By Acute and Chronic Ethanol. Alcohol Clin Exp Res. 2018;42(11):2186-2195. PubMed PMID: 30204234.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glutamate Transmission to Ventral Tegmental Area GABA Neurons Is Altered by Acute and Chronic Ethanol. AU - Williams,Stephanie B, AU - Yorgason,Jordan T, AU - Nelson,Ashley C, AU - Lewis,Natalie, AU - Nufer,Teresa M, AU - Edwards,Jeff G, AU - Steffensen,Scott C, Y1 - 2018/10/03/ PY - 2018/05/10/received PY - 2018/08/27/accepted PY - 2018/9/12/pubmed PY - 2019/11/7/medline PY - 2018/9/12/entrez KW - GABA KW - Ethanol KW - Glutamate KW - Ventral Tegmental Area SP - 2186 EP - 2195 JF - Alcoholism, clinical and experimental research JO - Alcohol. Clin. Exp. Res. VL - 42 IS - 11 N2 - BACKGROUND: Ventral tegmental area (VTA) GABA neurons have been heavily implicated in alcohol reinforcement and reward. In animals that self-administer alcohol, VTA GABA neurons exhibit increased excitability that may contribute to alcohol's rewarding effects. The present study investigated the effects of acute and chronic ethanol exposure on glutamate (GLU) synaptic transmission to VTA GABA neurons. METHODS: Whole-cell recordings of evoked, spontaneous, and miniature excitatory postsynaptic currents (eEPSCs, sEPSCs, and mEPSCs, respectively) were performed on identified GABA neurons in the VTA of GAD67-GFP+ transgenic mice. Three ethanol exposure paradigms were used: acute ethanol superfusion; a single ethanol injection; and chronic vapor exposure. RESULTS: Acute ethanol superfusion increased the frequency of EPSCs but inhibited mEPSC frequency and amplitude. During withdrawal from a single injection of ethanol, the frequency of sEPSCs was lower than saline controls. There was no difference in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/N-methyl-d-aspartate (NMDA) ratio between neurons following withdrawal from a single exposure to ethanol. However, following withdrawal from chronic ethanol, sEPSCs and mEPSCs had a greater frequency than air controls. There was no difference in AMPA/NMDA ratio following chronic ethanol. CONCLUSIONS: These results suggest that presynaptic mechanisms involving local circuit GLU neurons, and not GLU receptors, contribute to adaptations in VTA GABA neuron excitability that accrue to ethanol exposure, which may contribute to the rewarding properties of alcohol via their regulation of mesolimbic dopamine transmission. SN - 1530-0277 UR - https://www.unboundmedicine.com/medline/citation/30204234/Glutamate_Transmission_to_Ventral_Tegmental_Area_GABA_Neurons_Is_Altered_by_Acute_and_Chronic_Ethanol_ L2 - https://doi.org/10.1111/acer.13883 DB - PRIME DP - Unbound Medicine ER -