Ethanol Induces Persistent Potentiation of 5-HT Receptor-stimulated GABA Release at Synapses on Rat Hippocampal CA1 Neurons

Overview

Journal Neuropharmacology

Specialties Neurology
Pharmacology

Date 2020 Dec 4

PMID 33275959

Citations 2

Authors

Sang Beom Jun

Stephen R Ikeda

Jee Eun Sung

David M Lovinger

Affiliations

Soon will be listed here.

Abstract

Several studies have shown that ethanol (EtOH) can enhance the activity of GABAergic synapses via presynaptic mechanisms, including in hippocampal CA1 neurons. The serotonin type 3 receptor (5-HT-R) has been implicated in the neural actions of ethanol (EtOH) and in modulation of GABA release from presynaptic terminals. In the present study, we investigated EtOH modulation of GABA release induced by 5-HT-R activation using the mechanically isolated neuron/bouton preparation from the rat CA1 hippocampal subregion. EtOH application before and during exposure to the selective 5-HT receptor agonist, m-chlorophenylbiguanide (mCPBG) potentiated the mCPBG-induced increases in the peak frequency and charge transfer of spontaneous GABAergic inhibitory postsynaptic currents. Interestingly, the potentiation was maintained even after EtOH was removed from the preparation. A protein kinase A inhibitor reduced the magnitude of EtOH potentiation. Fluorescent Ca imaging showed that Ca transients in the presynaptic terminals increased during EtOH exposure. These findings indicate that EtOH produces long-lasting potentiation of 5-HT-induced GABA release by modulating calcium levels, via a process involving cAMP-mediated signaling in presynaptic terminals.

Citing Articles

Alcohol Use Disorder: Neurobiology and Therapeutics.

Yang W, Singla R, Maheshwari O, Fontaine C, Gil-Mohapel J Biomedicines. 2022; 10(5).

PMID: 35625928 PMC: 9139063. DOI: 10.3390/biomedicines10051192.

Local modulation by presynaptic receptors controls neuronal communication and behaviour.

Lovinger D, Mateo Y, Johnson K, Engi S, Antonazzo M, Cheer J Nat Rev Neurosci. 2022; 23(4):191-203.

PMID: 35228740 PMC: 10709822. DOI: 10.1038/s41583-022-00561-0.

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