Effects of inflammatory nociceptive stimulation in newborn rats: behavioral and neurobiological changes and behavioral consequences in adulthood

Abstract

Invasive painful procedures are often performed in neonates admitted into intensive care units (ICU). The acute and long-term stimulation caused by these procedures can be investigated in animal models, such as newborn rats. Previous studies have shown that animals subjected to noxious stimulation in the neonatal period have behavioral changes, such as signs of anxiety or depression. Under the same conditions, neonatal stimuli also lead to increase in neurogenesis rate and cellular activation in the hippocampus. Thus, it is of great interest to investigate whether such cellular alterations can be correlated to the behavioral changes. It is also true that stressful events in adulthood can bring out behavioral manifestations that once were in latent state; and stressful events in critical periods of development can undermine the resilience mechanisms to stress. In this scenario, the study proposal has been designed over three lines investigation from the neonatal nociceptive stimulation (induced in the first or eighth day after birth, with the intraplantar injection of CFA Freund's adjuvant -complete): I - behavioral parameters indicative of like-anxious and depressive-like behaviors after the challenge (movement restriction stress); II - analysis of sleep parameters (macro and micro-architecture) at baseline conditions, post-stress and after the sleep deprivation (homeostatic response); III - cellular mechanisms involved, such electrophysiological analysis of the hippocampus (LTP), central monoamines, receptors expression (5-HT1A) and signaling factors (p-CREB) in key structures involved in the emotional behavior regulation. (AU)