Female rats are resistant to the long-lasting neurobehavioral changes induced by adolescent stress exposure

Stress during adolescence is a risk factor for neuropsychiatric diseases, including schizophrenia. We recently observed that peripubertal male rats exposed to a combination of daily footshock plus restraint stress exhibited schizophrenia-like changes. However, numerous studies have shown sex differences in neuropsychiatric diseases as well as on the impact of coping with stress. Thus, we decided to evaluate, in adolescent female rats, the impact of different stressors (restraint stress [RS], footshock [FS], or the combination of FS and RS [FS+RS]) on social interaction (3-chamber social approach test/SAT), anxiety responses (elevated plus-maze/EPM), cognitive function (novel object recognition test/NOR), and dopamine (DA) system responsivity by evaluating locomotor response to amphetamine and in vivo extracellular single unit recordings of DA neurons in the ventral tegmental area (VTA) in adulthood. The impact of FS+RS during early adulthood was also investigated. Adolescent stress had no impact on social behavior, anxiety, cognition and locomotor response to amphetamine. In addition, adolescent stress did not induce long-lasting changes in VTA DA system activity. However, a decrease in the firing rate of VTA DA neurons was found 1-2 weeks post-adolescent stress. Similar to adolescent stress, adult stress did not induce long-lasting behavioral deficits and changes in VTA DA system activity, but FS+RS decreased VTA DA neuron population activity 1-2 weeks post-adult stress. Our results are consistent with previous studies showing that female rodents appear to be more resilient to developmental stress-induced persistent changes than males and may contribute to the delayed onset and lesser severity of schizophrenia in females.