Postnatal social stress impairs cognitive function, while acute methamphetamine enhances performance in adult male rats.

Methamphetamine (MA) is a potent psychostimulant frequently abused during pregnancy, with potential long-term consequences for offspring neurodevelopment. In addition to prenatal exposure, early-life stress is a critical factor influencing cognitive function in adulthood. This study aimed to evaluate the combined effects of prenatal MA or injection stress, early postnatal stressors (social and/or physical), and acute MA administration in adulthood on cognitive performance in male rats. Pregnant female Wistar rats received MA (5 mg/kg, s.c.), saline (1 ml/kg, s.c.), or no treatment throughout gestation. Offspring were exposed to postnatal stressors during PD 1-21, including maternal separation (S), maternal cold-water stress (W), a combination of both (SW), or no stress (N). In adulthood (PN 60-80), male offspring were tested in the Morris Water Maze (MWM) and received daily acute MA (1 mg/kg) or saline following testing. Prenatal MA or injection stress had minimal impact on spatial learning and memory. In contrast, early postnatal social stress (maternal separation) significantly impaired performance across MWM tasks, as reflected by increased latency, search error, and maladaptive search strategies. Acute MA administration in adulthood improved cognitive performance, particularly in animals previously exposed to postnatal social stress, where it attenuated stress-associated deficits. However, performance enhancement was also observed in non-stressed controls, indicating a general cognitive-enhancing effect. Overall, early postnatal social stress exerts a stronger negative effect on cognitive function than prenatal factors in this model. Acute low-dose MA enhances performance in spatial tasks and partially mitigates stress-related deficits, but its effects are not limited to previously impaired animals. These findings highlight the importance of early-life environment in shaping adult cognitive outcomes and suggest possible context-dependent effects of psychostimulant exposure.