Neonatal tactile stimulation decreases depression‐like and anxiety‐like behaviors and potentiates sertraline action in young rats

Abstract

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.

Tactile stimulation during different developmental periods modifies hippocampal BDNF and GR, affecting memory and behavior in adult rats

“…Taking into account the reduction in CORT levels and the behavioral results obtained in EPM and DBT, we can state that TS is able to reduce emotionality, anxiety and fear‐like symptoms during adult life by regulating HPA axis activity. These results are in accordance with a recent study by our laboratory in which TS has shown its beneficial effect by reducing CORT and cortisol, which are regulated in the same way and simultaneously released in animals submitted to a depression‐like protocol (Freitas et al, ).…”

“…Interestingly, these outcomes would support the hypothesis of a better regulation of anxiety behaviors through high GR immunocontent in the hippocampus as suggested by Sampedro‐Piquero et al (). Considering these findings, we can confirm that TS is able to mimic anxiolytic and antidepressant drug effects as recently shown (Boufleur et al, ; Freitas et al, ).…”

“…The beneficial influence of TS on anxiety parameters, as observed here, is well known and previous studies performed by our group evidenced similar behaviors in rats exposed to TS (Boufleur et al, ; Antoniazzi et al, , 2014b; Freitas et al, ). These TS results reinforce the anxiolytic properties of this procedure, that reduces emotionality in adult animals thereby improving their ability to cope with stressful situations.…”

Neonatal Tactile Stimulations Affect Genetic Generalized Epilepsy and Comorbid Depression-Like Behaviors

“…First, BDNF is involved in the origin of depression and in antidepressant effects and NTS enhanced BDNF ( Martinowich et al, 2007 ; Antoniazzi et al, 2017 ). Next, NTS decreased depression-like behavior later in life ( Freitas et al, 2015 ): TS early in life was accompanied by an increase in active swimming time and a decrease in immobility time in FST. Handling in animals resulted in different behavioral, endocrinological and neurochemical adaptive responses, suggesting the involvement of various neural pathways.…”

“…Neonatal TS enriches the experience and improves maturation of newborn animals, positively influencing behaviors and neuroendocrine systems in pups ( Boufleur et al, 2012 , 2013 ; Antoniazzi et al, 2014 ). Others showed that neonatal TS increases neurogenesis and neuroplasticity, improves anxiety-like behaviors and prevents depression-like behaviors ( Richards et al, 2012 ; Freitas et al, 2015 ; Roversi et al, 2019 ). Recent reports have shown that when TS is applied both during the initial periods of development and in adult rats, neurotrophins such as brain-derived neurotrophic factor (BDNF) and fibroblast growth factor 2 (FGF-2) increase in different brain areas.…”