Long-Term Effects of Chronic Buspirone during Adolescence Reduce the Adverse Influences of Neonatal Inflammatory Pain and Stress on Adaptive Behavior in Adult Male Rats.

Irina P Butkevich,Elena A Vershinina,Gordon A Barr,Anna M Aloisi,Viktor A Mikhailenko

doi:10.3389/fnbeh.2017.00011

Abstract

Neonatal pain and stress induce long-term changes in pain sensitivity and behavior. Previously we found alterations in pain sensitivity in adolescent rats exposed to early-life adverse events. We tested whether these alterations have long-lasting effects and if those effects can be improved by the 5-hydroxytryptamine 1A (5-HT1A) receptor agonist buspirone injected chronically during the adolescent period. This study investigates: (1) effects of inflammatory pain (the injection of formalin into the pad of a hind paw) or stress (short maternal deprivation-isolation, MI), or their combination in 1–2-day-old rats on the adult basal pain, formalin-induced pain, anxiety and depression; (2) effects of adolescent buspirone in adult rats that experienced similar early-life insults. Changes in nociceptive thresholds were evaluated using the hot plate (HP) and formalin tests; levels of anxiety and depression were assessed with the elevated plus maze and forced swim tests respectively. Both neonatal painful and stressful treatments induced long-term alterations in the forced swim test. Other changes in adult behavioral responses were dependent on the type of neonatal treatment. There was a notable lack of long-term effects of the combination of early inflammatory pain and stress of MI on the pain responses, anxiety levels or on the effects of adolescent buspirone. This study provides the first evidence that chronic injection of buspirone in adolescent rats alters antinociceptive and anxiolytic effects limited to adult rats that showed behavioral alterations induced by early-life adverse treatments. These data highlight the role of 5-HT1A receptors in long-term effects of neonatal inflammatory pain and stress of short MI on adaptive behavior and possibility of correction of the pain and psychoemotional behavior that were altered by adverse pain/stress intervention using buspirone during critical adolescent period.

Highlights

IntroductionClinical and laboratory findings indicate that early-life painful and stressful events result in unfavorable neurodevelopmental outcomes: adult animals demonstrate increased sensitivity to clinical and experimental stimuli (Anand et al, 1999; Ren et al, 2004; Grunau, 2013; Walker et al, 2016), altered function of the hypothalamo-pituitary-adrenal axis (HPA) and behavioral changes (Anseloni et al, 2005; Rincón-Cortés and Sullivan, 2014; Brummelte et al, 2015; Valeri et al, 2015; Victoria and Murphy, 2016)
Licking duration was not altered in adult rats that had experienced the combination of pain and stress on P1, 2; their licking duration was significantly lower than in the maternal deprivation-isolation (MI) group (p = 0.011; Figure 2B)
The present study demonstrates that repeated inflammatory pain and stress in neonatal rats induce long-term alterations in adaptive behaviors depending on the type of treatment

Summary

Introduction

Clinical and laboratory findings indicate that early-life painful and stressful events result in unfavorable neurodevelopmental outcomes: adult animals demonstrate increased sensitivity to clinical and experimental stimuli (Anand et al, 1999; Ren et al, 2004; Grunau, 2013; Walker et al, 2016), altered function of the hypothalamo-pituitary-adrenal axis (HPA) and behavioral changes (Anseloni et al, 2005; Rincón-Cortés and Sullivan, 2014; Brummelte et al, 2015; Valeri et al, 2015; Victoria and Murphy, 2016). Pain in newborn children in the neonatal intensive care unit is accompanied by the stress of separation from the mother (maternal deprivation). The mechanisms of long-term influences of early-life pain and stress on nociception and stress responses are not known and are the subject of much clinical and basic research (Schwaller and Fitzgerald, 2014; Brummelte et al, 2015; Victoria and Murphy, 2016; Walker et al, 2016)

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