Prenatal experience and postnatal stress modulate the adult neurosteroid and catecholaminergic stress responses

Allopregnanolone (3 alpha-hydroxy-5 alpha-regnan-20-one) is a neuroactive steroid recently shown to be involved in the neurochemical stress response via its positive modulation of the GABAA receptor complex. This experiment investigated the effects of postnatal stress (daily maternal separation during the first week of life) on the subsequent adult response to a stressor (10 min forced swim) in Long-Evans rats from one of three prenatal treatment groups (alcohol, pair-fed and control). Indices of stress response were allopregnanolone concentrations in plasma, cortex and hippocampus, and dopamine and norepinephrine concentrations in prefrontal cortex, nucleus accumbens and striatum. Females had higher levels of allopregnanolone than males in both plasma and brain. Prenatal alcohol exposure combined with early maternal separation stress resulted in an increase in the endogenous levels of allopregnanolone in the prefrontal cortex and hippocampus of adult offspring in response to a stressor compared to subjects without a prior history of postnatal stress; this effect was greater in females. This increased allopregnanolone was also associated with decreased dopamine and norepinephrine levels in the prefrontal cortex. In the prenatal alcohol-exposed offspring, postnatal maternal separation blunted the increase in dopamine levels in the striatum seen in both control groups. Postnatal maternal separation increased norepinephrine levels in the nucleus accumbens regardless of prenatal experience, while in the prefrontal cortex only prenatal diet condition (pair-feeding and alcohol) resulted in lower norepinephrine levels. The results of this experiment suggest that experience, both pre- and postnatal, can have long-term consequences for the developing neurochemical responses to stressors.