Objective      To determine the effect of melanocortin-4 receptor (MC4R) on the epileptogenesis and to discover the potential mechanism involved.        Methods      Fifty-two male SD rats were divided into a control group and 7 experimental groups (6

24 and 72 h

7

14

30 and 60 d). Western bloting

immunohistochemistry

and double-labelled immunofluorescence assay were then applied to detect the dynamic change of the expression pattern of MC4R in the brain tissue of the pilocarpine kindled rats. Forty male SD rats were then divided into the control

pentylenetetrazol (PTZ)

PTZ+0.9%NaCl

and PTZ+0.9%NaCl+HS014 (a specific inhibitor to MC4R) groups. The sub-convulsion dosage of PTZ was applied every other day for 29 d to establish the chronically kindled models and observe the kindling scores

and the latency and duration of generalized tonic-clonic seizure (GTCS) of each group. All animals were sacrificed on the 28th day after the models were established

and the expression of phspo-GluR1 (Ser 845) in the brain tissue of the rats in each group was detected by Western blotting.       Results      The MC4R expression was significantly increased in the brain tissue of the pilocarpine kindled rats at each time point as compared with the control group (P0.05)

and the peak occurred on the 14th day (P0.01). The MC4R inhibitor HS014 significantly decreased the kindling scores (P0.05) and prolonged the onset latency (P0.05) of GTCS in the rats during the PTZ chronic kindling process. The expression of phspo-GluR1 (Ser 845) of the HS014 treated group was decreased as compared with the PTZ group (P0.05).       Conclusion      Over-expression of MC4R might participate in the process of epileptogenesis via facilitating the phosphorylation process of GluR1 (Ser 845).