EFEITOS DA ADMINISTRAÇÃO DE L-ARGININA E CREATINA SOBRE PARÂMETROS COMPORTAMENTAIS DE RATOS SUBMETIDOS A UM MODELO DE ESTRESSE CRÔNICO VARIADO

Abstract

This research aimed to investigate the effects of administration of L-arginine and creatine on behavioral, biochemical, nutritional and anatomical parameters in rats submitted to a model of chronic variable stress. The study included 35 male Wistar rats, having approximately 120 days at the beginning of the experiments. The animals were divided equally and randomly into five groups: control (Ct), chronic stress (Ec); chronic stress + L-arginine (Ec/La); chronic stress + creatine (Ec/Cr) and chronic stress + L-arginine + creatine (Ec/La+Cr). The animals were exposed to stress for a period of 40 days and daily and randomly one of the following stressors were applied: crowded environment, exposure to cold, restraint, inclination of home cage, flashing light, food deprivation and noise. One day after the last stress session, the animals were subjected to the following behavioral tasks: elevated plus maze, open field task, measurement of palatable food intake and the Morris water maze test. The day after the last behavioral test session, the animals were sacrificed by decapitation, trunk blood was collected for biochemical analysis (glucose, cholesterol, triglycerides and corticosterone) and the heart, liver, adipose tissue (mesenteric, retroperitoneal and periepididymal fat), left kidney and adrenal gland were weighed. The results showed that the animals in group Ec, while consuming larger amounts of food and water, had lower body weight gain and showed other important biological markers of chronic stress (eg. lower liver weight and high blood glucose), also showing anxiety in the elevated plus maze and locomotor impairment in open field task. No treatment was able to reduce the effects of stress on feed/water intake and glucose, but all minimized the damage in the locomotor activity and increased consumption of palatable food (Froot Loops®). Treatment with L-arginine provoked cardiac hypertrophy. Creatine alone decreased the relative weight of the left adrenal gland, prevented body and liver loss weight and promoted a superior performance on spatial working memory. Coadministration of L-arginine and creatine provided a significant reduction in the relative weight of the adipose tissue and adrenal gland, blocked the hypertrophic cardiac effects of L-arginine, reduced anxiety in the elevated plus maze and has enable the occurrence of spatial learning in a training protocol that did not promote learning in group Ct. In conclusion, this study showed that coadministration of L-arginine and creatine provides improvement in all behavioral parameters evaluated, demonstrating superiority over the separate administration of these substances.