Effects of melatonin on excitability of pyramidal neurons in prefrontal cortex and the role of MT1R-cAMP-PKA signaling pathway

Objective To evaluate the effects of melatonin on the excitability of pyramidal neurons in the prefrontal cortex and the role of melatonin receptor 1 (MT1R)-cyclic adenosine monophosphate(cAMP)-protein kinase A (PKA) signaling pathway. Methods Brains were obtained from male Sprague-Dawley rats between 14 and 21 days after birth.The brain slices of 350-μm thick were prepared and placed in artificial cerebrospinal fluid.The brain slices were divided into 5 groups(n=6 each) using a random number table method: control group (C group), melatonin group (M group), MT1/2R antagonist luzindole plus melatonin group (L+ M group), MT2R antagonist 4P-PDOT plus melatonin group (P+ M group) and PKA inhibitor Rp-cAMPS plus melatonin group (R+ M group). Cells were perfused for 2 min with artificial cerebrospinal fluid in group C. Cells were perfused for 2 min with 1 μmol/L melatonin in group M. Cells were perfused for 2 min with the mixture of 1 μmol/L MT1/2R antagonist luzindole and 1 μmol/L melatonin in group L+ M.Cells were perfused for 2 min with the mixture of 1 μmol/L MT2R antagonist 4P-PDOT and 1 μmol/L melatonin in group P+ M.In group R+ M, 1 mmol/L PKA inhibitor Rp-cAMPS was continuously added to the pipette solution, and cells were perfused for 2 min with 1 μmol/L melatonin.The whole-cell patch-clamp technique was used to record the membrane potential and clamp current of pyramidal neurons in the prefrontal cortex. Results Compared with group C, the clamp current was significantly increased, and the membrane potential was decreased in group M(P 0.05). Conclusion Melatonin inhibits the excitability of pyramidal neutrons in the prefrontal cortex, and the mechanism is related to activating MT1R-cAMP-PKA signaling pathway. Key words: Melatonin; Neurons; Receptors, melation, MT1; Cyclic AMP; Protein kinases