Effect of melatonin on the regulation of proenkephalin and prodynorphin mRNA levels induced by kainic acid in the rat hippocampus

The in vivo short-term effect of melatonin on kainic acid (KA)-induced proe nkephalin (proENK) or prodynorphin (proDYN) mRNA, and on AP-1 protein level s in the rat hippocampus, were studied. Melatonin (5 mg/kg) or saline was a dministered intraperitoneally (i.p.) to rats 30 min prior to and immediatel y after i.p. injection of KA (10 mg/kg). Rats were sacrificed 1 and 3 h aft er KA injection. The proENK and proDYN mRNA levels were significantly incre ased 3 h after KA administration. The elevations of both proENK and proDYN mRNA levels induced by KA were significantly inhibited by the preadministra tion with melatonin. The increases of proENK and proDYN mRNA levels induced by KA were well-correlated with the increases of c-Fos, Fra-2, FosB, c-Jun , and JunB protein levels, which were significantly increased 3 h after KA administration and effectively inhibited by administration with melatonin. In an electrophoretic mobility shift assay, both AP-1 and ENKCRE-2 DNA bind ing activities were increased by KA, which were also attenuated by the admi nistration of melatonin. In addition, cross-competition studies revealed th at AP-1 or ENKCRE-2 DNA binding activity was effectively reduced by the 50x unlabeled cross-competitor. Therefore, these data suggest that melatonin h as an inhibitory role in KA-induced gene expression, such as proENK and pro DYN mRNA expression, and this may be due to a reduction of KA-induced AP-1 or ENKCRE-2 DNA binding activity. (C) 2000 Wiley-Liss, Inc.