The effects of rapamycin on maternal aggression in rats

In modern medicine, mTOR (mammalian target of rapamycin) inhibitör rapamycin is used as a immunosuppressive agent, and it is effective on cancer treatment, retarding aging, neuron-protective and antiinflammatory. Studies about the effects of rapamycin on nervous system has been shown that rapamycin organized regulation of mTOR. In addition the mTOR pathway may have significance in the underlying molecular mechanism leading to aggression associated with epilepsy. Generally, lactating female mammals exhibit an aggressive behavior, which is called maternal aggression, to protect their pups towards intruders to the nesting area. Aim of this study is to investigate acute effects of mTOR inhibitor rapamycin on maternal aggression in rats. In this maternal aggresion model, 63 Wistar female rats who have recently given birth were used. The animals were divided into 3 groups which are solvent (DMSO), 5 mg/kg rapamycin, and 10 mg/kg rapamycin. Then one of each group divided into two subgroup, and these subgroups consist 8 Wistar female rats. In order to eliminate the sequence effect of substances crossover experimental setup were used. After the postpartum Day 2 and 3, before 30 minutes starting to experiment saline solution applied intraperitoneally to control group, 5 mg/kg rapamycin applied to 5 mg/kg rapamycin group and 10 mg/kg rapamycin applied to 10 mg/kg rapamycin group as substance groups. Thirty minutes after injection of substances intruder rats will be placed into the home cage and then the aggressive behaviors of the resident rats observed and recorded by the camera for 20 minutes. 15 nonaggressive animals which did not display any aggressive behavior in both test days were removed from the experiment, and they were excluded from all further analysis. The groups will be compared in terms of the latency to the first aggressive behavior, the number of attacks, the total duration of aggressive behaviors and the severity of attack. When the groups compared in terms of the latency to the first aggressive behavior, it is found that 5 and 10 mg/kg doses of rapamycin prolong the latency significantly (in order of p=0.028 and p=0.024). As a result of evaluations in terms of the number of aggressive behaviors, it is found that 5 mg/kg rapamycin reduced number of attacks significantly (P=0.014). When the groups evaluated in terms of the total duration of aggressive behaviors, it is found that 5 mg/kg rapamycin shortened the time in terms of the exhibited aggresive behavior duration (P=0.033). Considering of severity of attack, it is found that 5 mg/kg rapamycin were given rats' severity of attacks were significantly lower than the saline groups (P=0.0125), but it is not found any differences between the other groups (p>0.05). According to these results, acute administration of rapamycin; especially in 5 mg/kg dose of rapamycin prolongs the maternal aggression latency in rats, and also 5 mg/kg dose of rapamycin decreased the number of attacks, the severity of attacks and the total duration of aggressive behaviors, and these results have shown that rapamycin has potential therapeutics effects which can be used on postpartum psychosis which is one of the most severe psychiatric disorder that can be seen during postpartum period. However it is necessary to conduct further studies in this area.