Changes and overlapping distribution in the expression of CB1/OX1-GPCRs in rat hippocampus by kainic acid-induced...

Status epilepticus (SE) is a life-threatening neurological disorder. It is important to discover new drugs to control SE without the development of pharmacoresistance. Focus on the cannabinoid receptor and cannabinoid-related compounds might be a good option. Cannabinoid receptor 1 (CB1) and orexin receptor 1 (OX1) both belong to the GPCR superfamily and display "cross-talk" interactions, however, there has been no study of the effect of OX1/CB1 in epilepsy. Therefore, we investigated the potential long-term effects of SE on CB1 and OX1 expression in rat hippocampus, aiming to elucidate whether they are involved in the causative mechanism of epilepsy and whether they might form a heterodimer. In this study, SE was induced with kainic acid, and results of immunohistochemistry and RT-PCR both showed that the expression of CB1 in the hippocampus increased after SE and was significantly higher compared to controls especially 1 week post-SE. However we did not find any significant difference in the expression of OX1 between the SE group and the controls at any time. Under immunofluorescence staining, we observed an overlapping distribution of CB1 and OX1 in the hippocampus. The increased expression of CB1 in the hippocampus indicates that CB1 may play an important role in the underlying mechanism of SE, but the effect of OX1 was not obvious. The overlapping distribution of CB1 and OX1 in the hippocampus indicates that they may form a heterodimer to exert their effect in epilepsy.