Early life nociceptive stimulus and fentanyl exposure increase hippocampal neurogenesis and anxiety but do not affect spatial learning and memory.

This study aimed to determine whether preemptive fentanyl administration in neonatal rats reduces the impact of a nociceptive stimulus initiated during the first day of life (P1) on hippocampal neurogenesis, behavior, and learning. At P1, Wistar rat pups received either a subcutaneous injection of fentanyl (F) before intraplantar injection of complete Freund's adjuvant (CFA) (CFA + F group), an isolated injection of CFA (CFA group), or subcutaneous injection of fentanyl without CFA injection (F). Control animals received saline injections using the same route and volume as the treatment groups. Hippocampal neurogenesis was evaluated by 5' -bromo-2'-deoxyuridine (BrdU) staining on P10 and P39 to assess neuronal proliferation and survival, respectively. Anxiety behavior in adulthood was assessed using an open field test (OF) and an elevated plus maze test (EPM). Spatial memory was assessed on a Morris water maze test (MWM), where the animals were trained for seven days, beginning on P81, and the probe trial was performed to evaluate memory retention. Although the CFA + F group showed an increased number of proliferative cells on P10, this finding did not persist on P39. The CFA + F group spent more time in the closed arms in the EPM, revealing more anxious behavior, although the early noxious experience, both with and without fentanyl, did not alter neurogenesis in adolescence and learning in adulthood. This study highlights that the impact of pain in early life pain combined with fentanyl on hippocampal neurogenesis on P10 did not persist on P39. In addition, this combined intervention during the first week of life was associated with higher anxiety levels.

Does neonatal manipulation on continuous or alternate days change maternal behavior?

Maternal separation and neonatal manipulation of pups produce changes in maternal behavior after the dam-pup reunion. Here, we examined whether continuous versus alternating days of neonatal manipulation during the first 8 postnatal days produces differential changes in maternal and non-maternal behaviors in rats. We found that both maternal separation protocols increased anogenital licking after dam-pup reunion, reflecting increased maternal care of pups.

LPS-Induced Systemic Neonatal Inflammation: Blockage of P2X7R by BBG Decreases Mortality on Rat Pups and Oxidative Stress in Hippocampus of Adult Rats.

Neonatal lipopolysaccharide (LPS) exposure-induced brain inflammation has been associated to neuronal injury and facilitates the development of models of neurological disorders in adult rats. The P2X7 receptor (P2X7R) plays a fundamental role in the onset and maintenance of the inflammatory cascade. Brilliant blue G (BBG), a P2X7R antagonist, has been shown to effectively promote neuroinflammatory protection. Here, we have investigated the long-term effects of the neonatal systemic inflammation on hippocampal oxidative stress, anxiety behavior and pain sensitivity in adulthood. We hypothesized that P2X7R blockade is able to modulate the effects of inflammation on these variables. Male and female rat pups received LPS and/or BBG solution intraperitoneally on the 1st, 3rd, 5th and 7th postnatal days. The survival rate and body weight were evaluated during the experimental procedures. The animals were submitted to behavioral tests for anxiety (elevated plus maze, EPM) and nociception (hot-plate and tail-flick) and the oxidative stress was measured by superoxide production in the dentate gyrus of the hippocampus using dihydroethidium (DHE) probe. BBG increased the survival rate in LPS-treated rats. No significant differences were found regarding anxiety behavior and pain sensitivity between the experimental groups. Systemic neonatal inflammation leads to a higher production of superoxide anion in the dentate gyrus of the hippocampus in adulthood and BBG inhibited that effect. Our data suggest that blocking the activation of the P2X7R during neonatal systemic inflammation may have a potential neuroprotective effect in adulthood.