Analysis of the Melanocortin Brain System of Krushinsky–Molodkina Rats with Genetic Predisposition to Audiogenic Seizures

The study was performed with 4-month-old male rats of the Krushinsky–Molodkina (KM) strain genetically predisposed to audiogenic seizures and Wistar rats, which are not sensitive to the effects of sound. In KM rats, real-time PCR revealed an increase in the level of AgRP mRNA (4-fold, p < 0.05) and melanocortin receptors MC4R (2.4-fold, p < 0.05) in the hypothalamus vs. Wistar rats. No differences in the level of proopiomelanocortin mRNA were detected. The results of immunohistochemical analysis indicate an increased (p < 0.05) level of optical density of AgRP, MC3R, and MC4R in the hypothalamic structures of KM rats vs. Wistar rats. In the dorsal hippocampus, a statistically significant increase in the level of MC3R (by Western blotting) and MC4R (by immunohistochemistry) was also detected in KM rats vs. Wistar rats. The obtained results are discussed in connection with the revealed blocking dose-dependent effect of SHU9119, a non-selective MC3R/MC4R inhibitor, on seizure activity in KM rats.