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Ethanol enhances glutamate transmission by retrograde dopamine signaling in a postsynaptic neuron/synaptic bouton preparation from the ventral tegmental area.
Neuropsychopharmacology. 2009 Apr; 34(5):1233-44.N

Abstract

It is well documented that somatodendritically released dopamine is important in the excitability and synaptic transmission of midbrain dopaminergic neurons. Recently we showed that in midbrain slices, acute ethanol exposure facilitates glutamatergic transmission onto dopaminergic neurons in the ventral tegmental area (VTA). The VTA is a brain region critical to the rewarding effects of abused drugs, including ethanol. We hypothesized that ethanol facilitation might result from an increase in somatodendritically released dopamine, which acts retrogradely on dopamine D(1) receptors on glutamate-releasing axons and consequently leads to an increase in glutamate release onto dopaminergic neurons. To further test this hypothesis and to examine whether ethanol facilitation can occur at the single-cell level, VTA neurons were freshly isolated from rat brains using an enzyme-free procedure. These isolated neurons retain functional synaptic terminals, including those that release glutamate. Spontaneous excitatory postsynaptic currents (sEPSCs) mediated by glutamate alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors were recorded from these freshly isolated putative dopaminergic neurons. We found that acute application of clinically relevant concentrations of ethanol (10-80 mM) significantly facilitated the frequency of sEPSCs but not their mean amplitude. Ethanol facilitation was mimicked by the D(1) agonist SKF 38393 and by the dopamine uptake blocker GBR 12935 but was blocked by the D(1) antagonist SKF 83566, and by depleting dopamine stores with reserpine, as well as by chelating postsynaptic calcium with BAPTA. Furthermore, the sodium channel blocker tetrodotoxin eliminated the facilitation of sEPSCs induced by ethanol but not by SKF 38393. These results constitute the first evidence from single isolated cells of ethanol facilitation of glutamate transmission to dopaminergic neurons in the VTA. In addition, we show that ethanol facilitation has a postsynaptic origin and a presynaptic locus. Furthermore, ethanol stimulation of a single dopaminergic neuron is capable of eliciting the release of somatodendritic dopamine, which is sufficient to influence glutamatergic transmission at individual synapses.

Authors+Show Affiliations

Department of Anesthesiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103-2714, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18784647

Citation

Deng, Chunyu, et al. "Ethanol Enhances Glutamate Transmission By Retrograde Dopamine Signaling in a Postsynaptic Neuron/synaptic Bouton Preparation From the Ventral Tegmental Area." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 34, no. 5, 2009, pp. 1233-44.
Deng C, Li KY, Zhou C, et al. Ethanol enhances glutamate transmission by retrograde dopamine signaling in a postsynaptic neuron/synaptic bouton preparation from the ventral tegmental area. Neuropsychopharmacology. 2009;34(5):1233-44.
Deng, C., Li, K. Y., Zhou, C., & Ye, J. H. (2009). Ethanol enhances glutamate transmission by retrograde dopamine signaling in a postsynaptic neuron/synaptic bouton preparation from the ventral tegmental area. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 34(5), 1233-44. https://doi.org/10.1038/npp.2008.143
Deng C, et al. Ethanol Enhances Glutamate Transmission By Retrograde Dopamine Signaling in a Postsynaptic Neuron/synaptic Bouton Preparation From the Ventral Tegmental Area. Neuropsychopharmacology. 2009;34(5):1233-44. PubMed PMID: 18784647.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ethanol enhances glutamate transmission by retrograde dopamine signaling in a postsynaptic neuron/synaptic bouton preparation from the ventral tegmental area. AU - Deng,Chunyu, AU - Li,Ke-Yong, AU - Zhou,Chunyi, AU - Ye,Jiang-Hong, Y1 - 2008/09/10/ PY - 2008/9/12/pubmed PY - 2009/5/8/medline PY - 2008/9/12/entrez SP - 1233 EP - 44 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 34 IS - 5 N2 - It is well documented that somatodendritically released dopamine is important in the excitability and synaptic transmission of midbrain dopaminergic neurons. Recently we showed that in midbrain slices, acute ethanol exposure facilitates glutamatergic transmission onto dopaminergic neurons in the ventral tegmental area (VTA). The VTA is a brain region critical to the rewarding effects of abused drugs, including ethanol. We hypothesized that ethanol facilitation might result from an increase in somatodendritically released dopamine, which acts retrogradely on dopamine D(1) receptors on glutamate-releasing axons and consequently leads to an increase in glutamate release onto dopaminergic neurons. To further test this hypothesis and to examine whether ethanol facilitation can occur at the single-cell level, VTA neurons were freshly isolated from rat brains using an enzyme-free procedure. These isolated neurons retain functional synaptic terminals, including those that release glutamate. Spontaneous excitatory postsynaptic currents (sEPSCs) mediated by glutamate alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors were recorded from these freshly isolated putative dopaminergic neurons. We found that acute application of clinically relevant concentrations of ethanol (10-80 mM) significantly facilitated the frequency of sEPSCs but not their mean amplitude. Ethanol facilitation was mimicked by the D(1) agonist SKF 38393 and by the dopamine uptake blocker GBR 12935 but was blocked by the D(1) antagonist SKF 83566, and by depleting dopamine stores with reserpine, as well as by chelating postsynaptic calcium with BAPTA. Furthermore, the sodium channel blocker tetrodotoxin eliminated the facilitation of sEPSCs induced by ethanol but not by SKF 38393. These results constitute the first evidence from single isolated cells of ethanol facilitation of glutamate transmission to dopaminergic neurons in the VTA. In addition, we show that ethanol facilitation has a postsynaptic origin and a presynaptic locus. Furthermore, ethanol stimulation of a single dopaminergic neuron is capable of eliciting the release of somatodendritic dopamine, which is sufficient to influence glutamatergic transmission at individual synapses. SN - 1740-634X UR - https://www.unboundmedicine.com/medline/citation/18784647/Ethanol_enhances_glutamate_transmission_by_retrograde_dopamine_signaling_in_a_postsynaptic_neuron/synaptic_bouton_preparation_from_the_ventral_tegmental_area_ L2 - http://dx.doi.org/10.1038/npp.2008.143 DB - PRIME DP - Unbound Medicine ER -