The effect of Intraventricular Injection of Kisspeptin-13 on Social Memory Deficits Induced by Methamphetamine

Methamphetamine is a stimulant of the central nervous system, which is now increasingly abused. Long-term use of this psychoactive drug is associated with many cognitive disorders, including learning and memory impairment. Kisspeptin-13 is one of the endogenous neuropeptides, whose neuroprotective role on cognitive functions, especially memory, was investigated in several studies. In the present study, the role of kisspeptin-13 in mitigating social memory impairment induced by methamphetamine was investigated.

This experimental study was carried out on 40 adult male Wistar rats weighing (200-270 g). This study was conducted with the code of ethics (IR.MAZUMS..REC.1398.6037) at the Neuroscience Research Center of Mazandaran University of Medical Sciences. In this study, the animals were randomly divided into four groups: control, methamphetamine,kisspeptin-13+ methamphetamine, and kisspeptin-13 groups. First, pretreatment with kisspeptin-13 was done intraventricularly for three days at a dose of 1.5 µg/µL in the respective groups. Specifically, on the initial day, the subjects were given a dose of 1 mg/kg twice, with a 4-hour interval. On the following day, the dosage was raised to 2 mg/kg, and this incrementally increased on subsequent days throughout the week. Thus, on the third day, the dose was 3 mg/kg, on the fourth day, the dose was 4 mg/kg, and on the fifth, sixth, and seventh days, the doses were 5 mg/kg, 6 mg/kg, and 7 mg/kg, respectively. After the injections, the social interaction behavioral test evaluates social memory and sociability. This test was carried out in a three-chambered device for ten minutes in a rectangular space that was divided into three parts. In the side chambers, there were two wire chambers in which stranger and familiar rats were placed. On the test day, the time spent in each room was monitored.

The results of this investigation, which examined the effect of kisspeptin-13 on sociability and social memory in two stages, were as follows. The effect of kisspeptin -13 on sociability showed that the duration of exploration in the chamber where the first stranger mouse was placed was longer than the duration of exploration in the empty chamber in all experimental groups. Results indicated that sociability in these animals was not affected by the administration of methamphetamine, as well as kisspeptin -13, and all animals in the groups receiving the drug responded similarly to the control group. Statistical analysis regarding the effect of kisspeptin -13 on social memory showed that there is a significant statistical difference in the time spent for the first stranger mouse and the second stranger mouse, and the animals in the group receiving methamphetamine spent more time in social interaction with the first stranger mouse, which indicates damage to social memory, and the administration of kisspeptin -13 in animals receiving methamphetamine also failed to improve social memory. In the group receiving kisspeptin -13, social memory was not significantly different from the control group, which indicated that the administration of kisspeptin -13 alone does not lead to damage to social memory.

This study showed that methamphetamine can lead to serious impairment of social memory without causing a change in social interaction, and pretreatment with kisspeptin-13 could not compensate for the damage to social memory caused by the administration of methamphetamine.