Sexual Dimorphism in the Effect of Neonatal Inflammatory Pain on Stress Reactivity of Hormonal Response and Cognitive Functions in Adult Rats

Abstract

The effect of moderate neonatal stress induced by inflammatory pain in rat pups of both sexes on the hormonal response and cognitive processes in adult animals was studied in the Morris water maze. No significant differences in spatial learning and memory were found in experimental rats exposed to neonatal inflammatory pain vs. control animals. However, experimental rats exhibited sex differences in long-term spatial memory whose efficiency was higher in males vs. females. After long-term memory testing, stress responsiveness of the hypothalamic-pituitary-adrenocortical axis, as assessed by the plasma corticosterone level in the formalin test, was higher in experimental males vs. females. Only experimental females exhibited differences between short-term and long-term memory, with the efficiency being higher in the former. Thus, sexual dimorphism was found in the effect of neonatal nociceptive stress on long-term spatial memory in adult rats: experimental males vs. females demonstrated more effective long-term memory combined with a higher stress reactivity of the hormonal response.

Keywords: adult rats; corticosterone; neonatal inflammatory pain; spatial learning and memory.

Fig. 1.

Latency to find a platform in the Morris water maze in the first trial for 5 training days and the second trial for 4 training days of spatial learning in male (a) and female (b) adult rats exposed to neonatal inflammatory pain, and in control rats. Abscissa: the numbers of trials (1, 2) and five training days. Columns a1–b1 and a2–b2 illustrate the results of statistical analysis on the first training day in trial 1 and trial 2 in males and females. Differences between experimental males and females on the first day in the first trial: a1–b1, significance level: p = 0.067; in the second trial: a2–b2, significance level: *p = 0.026.

Fig. 2.

Recording of short-term (1) and long-term (2) memory in the Morris water maze in adult male (a) and female (b) adult rats exposed to neonatal pain. Ordinate: time (s) spent in the target quadrant. White columns—control, dark columns—neonatal pain. Significance level: * p < 0.05, sexual differences in long-term memory in rats with neonatal pain; ⁺⁺ p < 0.01, short-term vs. long-term memory in females with neonatal pain.