It is well known that events which occur in early life exert a significant influence on brain development, what can be reflected throughout adulthood. This study was carried out in order to assess the influence of neonatal tactile stimulation (TS) on behavioral and morphological responses related to depression-like and anxiety-like behaviors, assessed following the administration of sertraline (SERT), a selective serotonin re-uptake inhibitor (SSRI). Male pups were submitted to daily TS, from postnatal day 8 (PND8) to postnatal day 14 (PND14), for 10 min every day. On PND50, adult animals were submitted to forced swimming training (15 min). On PND51, half of each experimental group (UH and TS) received a single sub-therapeutic dose of sertraline (SER, 0.3mg/kg body weight, i.p.) or its vehicle (C, control group). Thirty minutes after injection, depression-like behaviors were quantified in forced swimming test (FST, for 5 min). On the following day, anxiety-like behaviors were assessed in elevated plus maze (EPM), followed by biochemical assessments. TS per se increased swimming time, decreasing immobility time in FST. Besides, TS per se was able to increase frequency of head dipping and time spent in the open arms of EPM, resulting in decreased anxiety index. In addition, groups exposed to TS showed decreased plasma levels of corticosterone per se. Interestingly, while TS exposure significantly potentiated the antidepressant activity of a subtherapeutic dose of SERT, this drug was able to exacerbate TS-induced anxiolytic activity, as observed in FST and EPM, respectively. Decreased plasma levels of both corticosterone and cortisol in animals exposed to TS and treated with SERT are able to confirm the interesting interaction between this neonatal handling and the antidepressant drug. From our results, we conclude that neonatal TS is able to exert beneficial influence on the ability to cope with stressful situations in adulthood, preventing depression and favorably modulating the action of antidepressant drugs.

Recent studies have shown that tactile stimulation (TS) in pups is able to prevent and/or minimize fear, anxiety behaviors, and addiction to psychostimulant drugs in adult rats. In these studies, animals have been exposed to handling from postnatal day (PND) 1-21. This study was designed to precisely establish which period of preweaning development has a greater influence of TS on neuronal development. After birth, male pups were exposed to TS from PND1-7, PND8-14, and PND15-21. In adulthood, the different periods of postnatal TS were assessed through behavioral, biochemical, and molecular assessments. Animals that received TS from PND8-14 showed lower anxiety-like symptoms, as observed by decreased anxiety index in elevated plus maze. This same TS period was able to improve rats' working memory by increasing the percentage of alternation rate in Y-maze, and induce better ability to cope with stressful situations, as showed in the defensive burying test by a reduced time of burying behavior. On the other hand, animals receiving TS in the first week of life showed longest cumulative burying time, which is directly related to increased anxiety-like behavior. Moreover, TS from PND8-14 showed lower corticosterone levels and better oxidative status, as observed by decreased lipid peroxidation and increased catalase activity in the hippocampus. Brain-derived neurotrophic factor (BDNF) immunocontent was increased in the hippocampus of animals receiving TS from PND8-14, while glucocorticoid receptors immunocontent was decreased in both TS and TS , but not TS . To the best of our knowledge, this study is the first to show TS can be more efficient if applied over a focused period of neonatal development (PND8-14) and this beneficial influence can be reflected on reduced emotionality and increased ability to address stressful situations in adulthood. © 2016 Wiley Periodicals, Inc.

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