Long-Term Influences of Neonatal Pain-Related Stress on Cognitive and Stress-Hormonal Functions in Rats: Age and Sex Aspects

To address the problem of neonatal pain-related stress effectson spatial learning, memory and the stress reactivity of the hypothalamo-pituitary-adrenalaxis (the HPA) in adolescent and adult rats we gave male and femalerats an intraplantar injection of moderate concentration of formalin (2.5%,0.5 & mu;L) (Formalin rats) on postnatal days (P1 and P2). Adolescentmale Formalin rats showed expressed impairments in both learningand memory. Adult male and female Formalin rats displayed betterspatial learning than the adolescent Formalin rats; males, regardlessof age, revealed better ability in learning than females. AdultFormalin males showed higher HPA axis reactivity, which was combinedwith a higher performance of long-term memory compared with thecorresponding data in adult females. The data demonstrate that theconsequences of moderate neonatal pain-related stress manifestedthemselves in later life differently depending on the age and sex.Moreover, the results testify to an unconventional adaptive potentialof pain-related stress, which, when interacting with behavioralplasticity, improved the functioning of neurobiological systemsin adult rats. The identified sex differences in effects of pain-relatedstress on the cognitive functions in rats of both ages, as wellas the stress reactivity of hormonal response in adult rats, suggestsexual dimorphism in neonatal pain-triggered synaptic plasticityof structures involved in spatial learning and memory.