PRENATAL EXPERIENCE AND POSTNATAL STRESS MODULATE THE ADULT NEUROSTEROID AND CATECHOLAMINERGIC STRESS RESPONSES

Allopregnanolone (3 alpha-hydroxy-5 alpha-regnan-20-one) is a neuroact ive steroid recently shown to be involved in the neurochemical stress response via its positive modulation of the GABA, receptor complex. Th is experiment investigated the effects of postnatal stress (daily mate rnal separation during the first week of life) on the subsequent adult response to a stressor (10 min forced swim) in Long-Evens rats from o ne of three prenatal treatment groups (alcohol, pair-fed and control). Indices of stress response were allopregnanolone concentrations in pl asma, cortex and hippocampus, and dopamine and norepinephrine concentr ations in prefrontal cortex; nucleus accumbens and striatum. Females h ad higher levels of allopregnanolone than males in both plasma and bra in. Prenatal alcohol exposure combined with early maternal separation stress resulted in an increase in the endogenous levels of allopregnan olone in the prefrontal cortex and hippocampus of adult offspring in r esponse to a stressor compared to subjects without a prior history of postnatal stress; this effect was greater in females. This increased a llopregnanolone was also associated with decreased dopamine and norepi nephrine levels in the prefrontal cortex. In the prenatal alcohol-expo sed offspring, postnatal maternal separation blunted the increase in d opamine levels in the striatum seen in both control groups. Postnatal maternal separation increased norepinephrine levels in the nucleus acc umbens regardless of prenatal experience, while in the prefrontal cort ex only prenatal diet condition (pair-feeding and alcohol) resulted in lower norepinephrine revels. The results of this experiment suggest t hat experience, both pre- and postnatal, can have long-term consequenc es for the developing neurochemical responses to stressors. (C) 1998 I SDN. Published by Elsevier Science Ltd.