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Multiple sources of internal calcium stores mediate ethanol-induced presynaptic inhibitory GABA release in the central nucleus of the amygdala in mice.
Psychopharmacology (Berl). 2020 Nov; 237(11):3303-3314.P

Abstract

RATIONALE

Ethanol can enhance GABA release in various brain regions via presynaptic mechanisms. However, the presynaptic action of ethanol on inhibitory GABA release is still not well understood.

OBJECTIVES

Since calcium is required for neurotransmitter release from presynaptic terminals, the purpose of this study was to investigate the role of both internal and external calcium signaling in ethanol-induced enhancement of GABA release within the central amygdala nucleus (CeA) in acute brain slice preparations.

METHODS

Whole-cell patch clamp electrophysiology was used to record miniature GABAA receptor-mediated inhibitory postsynaptic currents (mIPSCs) from CeA neurons. Ethanol-enhanced mIPSCs were recorded in the presence of antagonists that regulate internal and external calcium-mediated processes.

RESULTS

Bath-applied ethanol dose-dependently increased the mean frequency of mIPSCs without altering mIPSC amplitude. Ethanol-induced increases in mIPSC frequency were antagonized by dantrolene, 2-APB, and the endoplasmic reticulum calcium pump (SERCA) antagonists thapsigargin and cyclopiazonic acid (CPA). Blocking calcium release from mitochondria or via exocytosis with ruthenium red also attenuated mIPSCs while frequency was not altered in the presence of a non-selective calcium channel blocker cadmium. The L-type calcium blocker nifedipine, but not its analogue nimodipine, blocked ethanol-induced enhancement in CeA neurons.

CONCLUSIONS

These results demonstrate ethanol-induced presynaptic release of GABA is mediated by internal calcium stores and by disrupting neurotransmitter exocytosis within the CeA, a critical brain area involved in drugs of abuse and alcohol addiction.

Authors+Show Affiliations

Addictions Division, Department of Psychiatry, Duke University Medical Center, Durham, NC, 27705, USA. VISN 6 MIRECC, Durham VA Medical Center, Durham, NC, 27705, USA.Addictions Division, Department of Psychiatry, Duke University Medical Center, Durham, NC, 27705, USA. VISN 6 MIRECC, Durham VA Medical Center, Durham, NC, 27705, USA.Addictions Division, Department of Psychiatry, Duke University Medical Center, Durham, NC, 27705, USA. sdmoore@duke.edu. VISN 6 MIRECC, Durham VA Medical Center, Durham, NC, 27705, USA. sdmoore@duke.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32705289

Citation

Li, Qiang, et al. "Multiple Sources of Internal Calcium Stores Mediate Ethanol-induced Presynaptic Inhibitory GABA Release in the Central Nucleus of the Amygdala in Mice." Psychopharmacology, vol. 237, no. 11, 2020, pp. 3303-3314.
Li Q, Klein RC, Moore SD. Multiple sources of internal calcium stores mediate ethanol-induced presynaptic inhibitory GABA release in the central nucleus of the amygdala in mice. Psychopharmacology (Berl). 2020;237(11):3303-3314.
Li, Q., Klein, R. C., & Moore, S. D. (2020). Multiple sources of internal calcium stores mediate ethanol-induced presynaptic inhibitory GABA release in the central nucleus of the amygdala in mice. Psychopharmacology, 237(11), 3303-3314. https://doi.org/10.1007/s00213-020-05613-w
Li Q, Klein RC, Moore SD. Multiple Sources of Internal Calcium Stores Mediate Ethanol-induced Presynaptic Inhibitory GABA Release in the Central Nucleus of the Amygdala in Mice. Psychopharmacology (Berl). 2020;237(11):3303-3314. PubMed PMID: 32705289.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multiple sources of internal calcium stores mediate ethanol-induced presynaptic inhibitory GABA release in the central nucleus of the amygdala in mice. AU - Li,Qiang, AU - Klein,Rebecca C, AU - Moore,Scott D, Y1 - 2020/07/24/ PY - 2020/01/29/received PY - 2020/07/17/accepted PY - 2020/7/25/pubmed PY - 2021/1/28/medline PY - 2020/7/25/entrez KW - Alcohol KW - Amygdala KW - GABA KW - Inhibitory postsynaptic currents KW - Internal calcium stores KW - Presynaptic release SP - 3303 EP - 3314 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 237 IS - 11 N2 - RATIONALE: Ethanol can enhance GABA release in various brain regions via presynaptic mechanisms. However, the presynaptic action of ethanol on inhibitory GABA release is still not well understood. OBJECTIVES: Since calcium is required for neurotransmitter release from presynaptic terminals, the purpose of this study was to investigate the role of both internal and external calcium signaling in ethanol-induced enhancement of GABA release within the central amygdala nucleus (CeA) in acute brain slice preparations. METHODS: Whole-cell patch clamp electrophysiology was used to record miniature GABAA receptor-mediated inhibitory postsynaptic currents (mIPSCs) from CeA neurons. Ethanol-enhanced mIPSCs were recorded in the presence of antagonists that regulate internal and external calcium-mediated processes. RESULTS: Bath-applied ethanol dose-dependently increased the mean frequency of mIPSCs without altering mIPSC amplitude. Ethanol-induced increases in mIPSC frequency were antagonized by dantrolene, 2-APB, and the endoplasmic reticulum calcium pump (SERCA) antagonists thapsigargin and cyclopiazonic acid (CPA). Blocking calcium release from mitochondria or via exocytosis with ruthenium red also attenuated mIPSCs while frequency was not altered in the presence of a non-selective calcium channel blocker cadmium. The L-type calcium blocker nifedipine, but not its analogue nimodipine, blocked ethanol-induced enhancement in CeA neurons. CONCLUSIONS: These results demonstrate ethanol-induced presynaptic release of GABA is mediated by internal calcium stores and by disrupting neurotransmitter exocytosis within the CeA, a critical brain area involved in drugs of abuse and alcohol addiction. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/32705289/Multiple_sources_of_internal_calcium_stores_mediate_ethanol_induced_presynaptic_inhibitory_GABA_release_in_the_central_nucleus_of_the_amygdala_in_mice_ L2 - https://dx.doi.org/10.1007/s00213-020-05613-w DB - PRIME DP - Unbound Medicine ER -