Análise comportamental de ratos Wistar machos em diferentes idades em um modelo de programação metabólica pela restrição protéica materna durante a lactação

Abstract

Neonatal undernutrition in rats results in short- and long-term metabolic and endocrine alterations in the offspring. It is known that some of these alterations, such as adrenal catecholamines content and hypercosticosterone, are associated with behavioral alterations in adult animals. However, it is not known whether these are present since the original insult or if these arise at some specific point after it. In this sense, in the present work, we analyzed, in Wistar rats, the effects of protein restriction programing during lactation on behavioral parameters associated with anxiety, locomotor activity and memory learning at different time points during development and maturation. Progenitors were separated into two groups after delivering: PR (protein restriction) group which received hipoproteic chow (8% protein) from birth to weaning [postnatal day (P) 21], and CONT (control) group which received normoprotein chow during this period. The following behavioral tests were used to analyze offspring behavior (21 animals per group per age) at P21, P45, P90 and P180: 1) elevated plus maze (EPM) used to assess anxiety related behaviors; 2) open field (OF) used to assess locomotor activity; 3) radial arm water maze (RAWM) used to assess memory and learning. After the behavioral tests, animals were decapitated and blood and the adrenal glands were collected for the analyses of catecholamine content and serum corticosterone level. In the EPM, PR animals had a significant increase in the values of the anxiety-associated variables when compared to the control group at P21. No differences were observed between groups at other time-points. In the OF, a significant reduction in the number of traversed rectangles was observed in the PR group at P90. No differences were observed between groups at other time-points. In the RAWM, we failed to identify significant differences between groups during the first four days of testing in all ages. On the fifth day (probe trial), the PR group had a significant reduction in the latency to find the scape platform at P21 and P180. As for the endocrine data, the PR group had a significant reduction in serum corticosterone level at P90. No differences were observed between groups at other time-points. Catecholamine content was increased in the RP group at P21 and P180. No differences were observed between groups at other time-points. Our data indicate that animals in the PR group display: 1) a reduction in anxiety-like behaviors at weaning; 2) a reduction in locomotor activity as young adults; 3) an improvement in memory/learning performance both at weaning and as mature adults. Additionally, our results indicate that there is an association between behavioral and endocrine alterations. We can conclude that protein restriction during lactation in rats affects behavior at different time points during the animal s life and that the temporal profile of the effects varies as a function of the behavior that is being assessed.