Differences in adaptive behaviors of adolescent male and female rats exposed at birth to inflammatory pain or stress

Abstract

In adolescent rats (25-35-day-old) exposed at birth (neonatal days 1 and, repeatedly, 2) to adverse impacts (inflammatory pain, short-term maternal separation stress, or both), sexual dimorphism was found in pain behavior under identical peripheral inflammation conditions. Our priority data indicate an enhancement of pain response in the formalin test in males, whereas in females pain sensitivity did not change, i.e. pain experienced in females at birth did not affect the system reactivity to the same chemical irritant in the adolescent period. However, rats of both sexes exposed to short-term maternal deprivation stress (60 min on neonatal days 1 and 2) exhibited the enhanced pain sensitivity in the formalin test. The combined impact of inflammatory pain and maternal deprivation in neonatal pups did not change pain sensitivity at adolescence both in males and females. Male and female rats exposed to early maternal deprivation exhibited decreased anxiety levels in the elevated plus-maze; rats exposed to each of the above-mentioned early impacts showed a decline in adaptive behavior in the forced swim test; males exposed to pain and combined impacts demonstrated the spatial learning impairment in the Morris labyrinth. Thus, we have pioneered in demonstrating sex-dependent differences in the effect of inflammatory pain in neonatal rat pups on the inflammatory pain sensitivity in adolescent rats. The division of early stress and pain impacts was revealed in adolescent females in the formalin test: while maternal deprivation induced hyperalgesia, pain did not change the tonic nociceptive system functional activity.

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

“…The behaviors in the HP test, formalin test and EPM in the rats of this group were unchanged, whereas the index of depression was significantly increased. This replicates our prior work showing that the combination of neonatal pain and stress in conditions of re-inflammation had no effect in adolescent rats (Butkevich et al, 2015 ). The means, by which there was a lower pain response in adult animals with greater overall neonatal adversity, are unknown but it is an important question in understanding the long-term effects of early pain and stress on adaptive behavior.…”

“…In Series I, male rats on P1 and on P2 (P1, 2) were exposed to the following treatments: a single injection of formalin (FOR group) or saline (control to formalin), after which the pups were immediately returned to their dams and siblings ( n = 11, n = 12 respectively); a single injection of FOR or saline and immediate isolation from the dams and siblings for 60 min (MI, “psychogenic stressor” (FOR followed by MI group), saline followed by MI group, n = 9, n = 9, respectively). The formalin concentration (2.5%), the volume of FOR or saline (0.5 μl), the site of injection (a single subcutaneous injection into the pad of the left hind paw) and the “psychogenic stressor” (each pup placed singly in a small cage in a thermostat at 30°C for 60 min) were similar to those in our previous work (Butkevich et al, 2015 ). The injection of FOR (but not that of saline) induced flexing and shaking of the injected paw, i.e., formalin-induced pain behavior (licking behavior is immature in neonatal pups).…”

“…Previously we found in 25-day-old rats morphological abnormalities in the nucleus raphe magnus following neonatal inflammatory pain that heightened hyperalgesia in the formalin test; structural characteristics were improved by chronic injections of buspirone and pain sensitivity was normalized when the rats reached late adolescence (Butkevich et al, 2015 ; Droblenkov et al, 2015 ). This nucleus is involved in the descending serotonergic system, which modulates nociceptive signals at the spinal cord dorsal horns and has neuroanatomical connections with the prefrontal cortex (Bernasconi et al, 2015 ) involved in psycho-emotional behavior.…”

“…Pain in newborn children in the neonatal intensive care unit is accompanied by the stress of separation from the mother (maternal deprivation). Using a rodent model of early-life pain, we previously found disrupted adaptive behavior in adolescent rats exposed as neonates to inflammatory pain or stress of maternal deprivation, with the consequences of early adverse insults dependent on the type and the age when they occur (Butkevich et al, 2015 ). In the present study, we use 1–2-day-old rats whose brain development is similar to that of a 24-week premature human infant (Anand et al, 1999 ; Schwaller and Fitzgerald, 2014 ).…”

Impact of Sexual Deprivation on Sexual Behavior and Some Reproductive-Endocrinal Functions in Albino Rats

“…In addition, the rat reproductive system and its hormonal control are a good model to study those changes in humans. Although there is no menstruation at the end of reproductive cycles in rats, structural and functional changes in the reproductive organs are closely related to those in humans (16).…”