The effects of Z56822977 on biosynthesis of serotonin in the brain of rats in the conditions of MSG-induced obesity

Abstract

Introduction: The present investigation aims to elucidate the effects of Z56822977 on biosynthesis of serotonin in the brain of rats in the conditions of monosodium glutamate (MSG)-induced obesity. Material and methods: Eighteen male rats were used in the present study and divided into three groups: 1 - control group, 2 - MSG group, 3 - MSG + Z56822977 group. Newborn rats of groups 2 and 3 were administered MSG dissolved in saline at the dose 4 mg/g body weight with a volume of 8 μl/g s.c. on days 2, 4, 6, 8, and 10 of life. Group 3 received an aqueous solution of Z56822977 a in dose 25 mg/kg at volume 1 ml/kg per os. Administration was started at the end of the fourth week after birth and continued intermittently by alternating a one-week course with three-week intervals of non-treatment. The MSG-group, respectively, received 1 ml/kg of water per os. Within four months after birth, rats were on a standard diet. The content of serotonin, tryptophan, 5-hydroxytryptophan (5-HTr), and activity of tryptophan hydroxylase (TRH), amino acid decarboxylase (AADC), and monoaminoxidase (MAO) were determined in brain tissue. Results: We have shown that administration of Z56822977 has a positive effect on the main indicators of obesity, as shown by changes in key physiological and biochemical parameters (body weight decreased by 13% vs. MSG (p < 0.05); body mass index (BMI), Lee index, and visceral fat mass decreased by 18%, 7%, and 55%, respectively (p < 0.05), in comparison with the MSG group). Content of tryptophan and serotonin significantly decreased (p < 0.05) in rats with MSG-induced obesity. Also, studies have shown an increase in MAO activity by 97% (p < 0.05) and decrease of TRH and AADC activity by 44% and 53%, respectively, (p < 0.05) in the brains of rats with obesity. Z56822977 increased the content of serotonin and tryptophan in rat brains and restored the activity of enzymes (MAO, TRH, AADC) to the control values. Conclusions: It is known that under conditions of obesity there is a disruption in the functioning of the serotonin system in the brains of rats. However, the administration of Z56822977 leads to normalisation of the serotonin and tryptophan content and normalisation of the activity of enzymes involved in the pathway of biosynthesis and the breakdown of serotonin. Thus, the administration of Z56822977, which affects the serotonergic system, can be used in the treatment of MSG-induced obesity in rats. Z56822977 can be considered as a possible novel therapeutic agent, but further studies are needed to confirm its action.