Depleção cerebral de serotonina durante o período neonatal programa a homeostase metabólica energética e a expressão comportamental de ratos adultos

Abstract

Brain serotonin (5-HT) depletion during the neonatal period lead a plastic cytoarchitecture change of the serotonergic system influencing directly several brain systems ontogeny development. This dissertation was aimed to elucidate the influence of brain 5-HT depletion during the neonatal period on the metabolic programming and the behavioral expression of adulthood rats. Brain 5-HT depletion was raised with the subcutaneous (s.c) administration of 100 mg. Kg-1 para-chlorophenylalanine (pCPA), a competitive inhibitor of the tryptophan hydroxylase enzyme, from the eighth at sixteenth post-natal days. In order to investigate the influence of pCPA on the subject metabolic programming, during and after treatment, the milk intake and body weight gain from the neonatal period to adulthood were evaluated. Furthermore, evaluating indirectly this influence on the energetic metabolism, the repercussions on the glycemic homeostasis through of the glycemia baseline measurements and under fasting in the adult rat were investigated. Around the ingestive behavior, baseline conditions paradigm and under fasting were made. In these experimental trials, water intake, ration, 2% sucrose and 0.3M NaCl were evaluated. Also, the 0.3 M NaCl intake after sodium depletion (furosemide 20mg. Kg-1, s.c) and water intake after hypertonic stimulus (1.0 M NaCl, s.c) were measured. The behavioral expression was evaluated through models involved with emotional-behavioral signals. In this analysis, the rat s anxiety status was investigated through of open field test, elevated plus-maze (EPM), social interaction and forced swimming. The results showed that treatment with pCPA reduces milk intake (P˂0.001) and therefore the body weight gain in the neonatal period (P˂0.001), claiming to be smaller until adulthood (P˂0.01). The glycemic homeostasis was also affected reflected in lower pCPA-male (P˂0.01) and pCPA-female (P˂0.001) levels after 24 hours of fasting. About to baseline intake, a higher pCPA-female sodium appetite (P˂0.05), related to a greater demand for 2% sucrose solution in both females (P˂0,001) were observed. Under fasting, a lower male-pCPA cumulative ration intake at 60 min (P˂0.05) and a higher female pCPA at 60 (P˂0.05) and 120 min (P˂0.01) were observed. Furthermore, after water deprivation, a higher pCPA-female cumulative water intake at 120 min (P˂0.05) compared with pCPA-male was rated. Was also observed a greater pCPA-male water intake at 120 and 180 min (P˂0.001) after hypertonic stimulus, however, it was not observed significant difference in the natriorexigenic responses in sodium depleted rats. In addition, pCPA male showed a evident anxiolytic activity in EPM test expressed by the higher time spent in the open arm (O.A) (P˂0.05), higher head-dipping in the O.A episodes (P˂0.001), less S.A.P. (P˂0.001) and grooming episodes (P˂0.01). Therefore, these results showed that 5-HT depletion during the neonatal period programme the energetic metabolic homeostasis and the behavioral expression of adulthood rats.