Melatonin potentiates the GABAA receptor-mediated current in cultured chick spinal cord neurons

The effect of melatonin on the γ-aminobutyric acid_A (GABA_A) receptor-mediated response was studied in cultured chick spinal cord neurons using the whole-cell voltage-clamp recording technique. Melatonin rapidly and reversibly potentiated the GABA-induced current in a dose-dependent fashion, with an EC₅₀ of 766 μM and a maximal potentiation of 148%. Potentiation of the GABA response by melatonin was mediated by increasing the potency of GABA rather than the efficacy. Prolonged exposure to a saturating concentration of the disulfide-reducing agent dithiothreitol did not attentuate the effect of melatonin on the GABA response, indicating that melatonin does not act through the redox site. Furthermore, our results demonstrate that melatonin and 5α-pregnan-3α-ol-20-one (a positive steroid modulator of the GABA_A receptor) act through different sites.