Sex-dependent changes in anxiety, memory, and monoamines following one week of stress

Chronic restraint stress alters performance of rats on cognitive tasks, and anxiety measurements, and these stress-induced behavioral alterations are sexually dimorphic. Following a long stress period (21 days restraint) males show cognitive impairments while females are either not affected or enhanced on the same tasks. The current study examined whether sexually differentiated responses are also induced following shorter restraint stress durations. Male and female Sprague Dawley rats, aged 2.5 months, served as controls or received restraint stress (6 h/day, 7 days) and were tested for anxiety (plus maze), non-spatial memory (object recognition), and spatial memory (object placement). Plus maze performance was altered by sex and stress exposure. Stress impaired male object recognition but did not affect female performance. Stress did not affect male spatial memory; however, control females could not significantly discriminate between the old and new locations, but stress exposure enhanced female performance. Following behavioral testing, monoamines and metabolites were measured in prefrontal cortex (PFC), hippocampus (CA1, CA3), and amygdala. Notably, PFC and CA3 indices for noradrenergic activity (MHPG levels and MHPG/NE ratios) were increased in stress females, but decreased in males, and similar changes were found in CA1 and BLA dopaminergic indices. Thus, these sexually dimorphic neurochemical changes following stress may underlie the behavioral differences. Current results show that short-term restraint elicits sex-dependent behavioral and neural changes different from those previously reported for longer term stresses and suggest that the temporal relationship between the change from adaptive to maladaptive responses to stress is shorter in male than female rats.