Abstract

In the present study, we investigated the effect of melatonin on the GABA-induced current (I(GABA) and GABAergic miniature inhibitory postsynaptic currents (mIPSCs) in cultured rat hippocampal neurons using the whole-cell patch-clamp technique. We found that melatonin rapidly and reversibly enhanced I(GABA) in a dose-dependent manner, with an EC50 of 949 μM. Melatonin markedly enhanced the peak amplitude of a subsaturating I(GABA) but not that of a saturating I(GABA). Interestingly, melatonin was effective only when GABA and melatonin were applied together. Furthermore, the effect of melatonin on I(GABA) was voltage-independent and did not change the ion selectivity of the GABA(A) receptor. The melatonin enhancement on I(GABA) can not be blocked by luzindole, a melatonin receptor antagonist, indicating that melatonin-induced I(GABA) enhancement was not via activation of its own membrane receptors. However, this enhancement may be mediated via high-affinity benzodiazepine sites as it was inhibited by the classical benzodiazepine antagonist flumazenil, suggesting an allosteric modulation of melatonin by binding to the sites of GABA(A) receptors. In addition, melatonin increased both amplitude and frequency of GABAergic mIPSCs, indicating that melatonin enhances GABAergic inhibitory transmission. Hence, our observation that melatonin has an enhancing effect on the GABAergic system may implicate a potential pathway for the neuroprotective effects of melatonin.

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Publisher Full Text

Authors

Cheng XP, Sun H, Ye ZY, Zhou JN

Institution

CAS Key Laboratory of Brain Function and Disease, and School of Life Sciences, University of Science and Technology of China, Hefei, PR China.

Source

Journal of pharmacological sciences 119:2 2012 pg 177-85

MeSH

Animals
Hippocampus
Inhibitory Postsynaptic Potentials
Melatonin
Neurons
Neuroprotective Agents
Pyramidal Cells
Rats
Rats, Wistar
Receptors, Melatonin
Tryptamines
gamma-Aminobutyric Acid

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22673185