Kainic acid-induced seizure activity alters the mRNA expression and G-protein activation of the opioid/nociceptin receptors in the rat brain cortex

Abstract

The opioid/nociceptin receptors are involved in many neurological disorders such as Alzheimer's disease, Parkinson's disease and epilepsy. Kainic acid (KA) is an analog of the excitatory amino acid transmitter glutamate and the systemic administration of KA induces status epilepticus (SE) in rodents. In this study, we examined the alterations in the G-protein activity and the gene expression levels of mu, kappa, delta opioid and nociceptin receptors (MOPr, KOPr, DOPr and NOPr) as well as PNOC, the precursor polypeptide of nociceptin-OFQ (N/OFQ) in KA-induced seizures in the rat brain cortex. KA was used to create seizures with the dose of 10 mg/kg body weight i.p. Following the KA administration, the rats were observed for 3 h to assess seizure activity. Seizures occurred approximately 45 min after the KA injection. Only rats exhibiting full limbic seizures, forelimb clonus with rearing, were used in this study. All animals were decapitated 4 h after the administration of KA. Our [(35)S]GTPγS binding results showed that there was a significant difference in both the affinity and efficacy particularly one of NOPr stimulation following KA treatment. Slight, but significant increase was observed for MOPr. Moreover PNOC, NOPr and MOPr mRNA levels were increased by KA treatment but there were no significant changes in the levels of DOPr and KOPr mRNAs. These results show that the activities of opioid/nociceptin receptors can be modified by KA-treatment, and MOPr, PNOC and NOPr are the most responsive to KA-induced seizures in the rat brain cortex.