Delta-opioid receptor-mediated modulation of excitability of individual hippocampal neurons: mechanisms involved

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Delta‑opioid receptor‑mediated modulation of excitability of individual hippocampal neurons: mechanisms involved Lucia Moravcikova1 · Roman Moravcik1,2 · Daniela Jezova3 · Lubica Lacinova1 · Eliyahu Dremencov1  Received: 7 April 2020 / Revised: 22 October 2020 / Accepted: 24 October 2020 © Maj Institute of Pharmacology Polish Academy of Sciences 2020

Abstract Background  Delta-opioid receptor (DOR)-mediated modulation of hippocampal neural networks is involved in emotions, cognition, and in pathophysiology and treatment of mood disorders. In this study, we examined the effects of DOR agonist (SNC80) and antagonist (naltrindole) on the excitability of individual hippocampal neurons. Methods  Primary neuronal cultures were prepared from hippocampi of newborn rats and cultivated in vitro for 8–14 days (DIV8-14). The effects of SNC80 naltrindole on evoked and spontaneous action potentials (APs) were measured at DIV8-9 and DIV13-14, respectively. Results  SNC80 (100 µM) potentiated spontaneous AP firing and stimulated sodium current; naltrindole had opposite effects. The stimulatory effect of 100 µM of SNC80 was revoked by pre-administration of 1 µM of naltrindole. SNC80 and naltrindole induced similar inhibitory effects on the evoked AP firing and on the calcium current. Further, SNC80 inhibited both peak and sustained potassium currents. Naltrindole had no effect on potassium currents. Conclusion  We suggest that the effects of naltrindole and high concentration of SNC80 on the sodium currents are mediated via DORs and underlying the changes in spontaneous activity. The inhibitory effects of SNC80 on calcium and potassium currents might also be DOR-dependent; these currents might mediate SNC80 effect on the evoked AP firing. The inhibitory effects of naltrindole on calcium and of low doses of SNC80 on sodium currents might be however DOR independent. The behavioral effects of SNC80 and naltrindole, observed in previous studies, might be mediated, at least in part, via the modulatory effect of these ligands on the excitability of hippocampal neurons. Keywords  Naltrindole · SNC80 · Sodium current · Potassium current · Calcium current

Introduction

Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s4344​0-020-00183​-2) contains supplementary material, which is available to authorized users. * Eliyahu Dremencov [email protected] 1



Institute of Molecular Physiology and Genetics, Center of Biosciences, Slovak Academy of Sciences, Bratislava, Slovakia

2



Department of Animal Physiology and Ethology, Faculty of Natural Sciences, Comenius University in Bratislava, Bratislava, Slovakia

3

Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia



Opioid receptors (ORs) are widely expressed in peripheral and central nervous system. Four types of ORs are known: µ- (MOR), κ- (KOR), and δ-opioid receptors (DOR) and nociception/orphanin FQ receptor. MORs and DORs are expressed in all parts of hip