The anticonvulsant effects of salmon calcitonin on pentylenetetrazole-kindled rats

Abstract

Epilepsy is a disorder of the brain, characterized by an enduring predisposition for the generation of epileptic seizures because of hyperexcitability and hypersynchrony of cortical neurons (Devinsky et al. 2014). Salmon calcitonin is a type of calcitonin with 32 amino acids. It is more potency than human calcitonin due to differences in its amino acid sequence (Masi et al. 2007). In the current study, we investigated the effects of salmon calcitonin on pentylenetetrazoleinduced seizures in kindled rats. In our study, 48 (240-260 g) male Wistar Albino rats were used. Rats were kindled by injections of a subconvulsant dose of pentylenetetrazole (35 mg/kg) once every other day for 15 times. Epileptic behaviors were observed for a period of 30 min. Seizure activity was scored, using the revised Racine’s scale. Rats that had seizure stages of 4 or 5 after three consecutive injections of PTZ were defined as fully kindled.  The kindled rats were divided into six groups (n=8 for each group) as saline (1 ml/kg saline), salmon calcitonin (25, 50 and 100 µg/kg), ethosuximide (100 mg/kg) and ethosuximide + salmon calcitonin. Electrodes were placed to animals’ skulls under stereotaxy to receive electroencephalography (EEG). After thirty minutes of administration of drugs, 35 mg/kg PTZ was given to induce seizures. EEG and video recordings of animals were taken simultaneously for thirty minutes. In the evaluation of the video and EEG recordings, the seizure stages of animals, the first myoclonic jerk time and the number of epileptic seizure spikes were calculated. Salmon calcitonin reduced seizures stage, epileptic seizure spikes and also prolonged first myoclonic jerk time compared to saline group. In addition, salmon calcitonin and ethosuximide combination decreased epileptic seizure spikes and increased the first myoclonic jerk time compare to ethosuximide group. In conclusion, salmon calcitonin decreased epileptic seizures and improved anticonvulsant effect of ethosuximide in the pentylentetrazole-kindled rat.