Prenatal stress and early adoption effects on benzodiazepine receptors and anxiogenic behavior in the adult rat brain

Abstract

Chronic maternal stress during pregnancy has been associated with behavioral alterations that persist into adulthood. Moreover, adoption procedures performed immediately after birth can reverse these alterations. In this study, we examined the effects of prenatal restraint stress and adoption at birth (cross-fostering) on the behavioral response to an anxiety-provoking situation and on the adult male offspring expression of benzodiazepine (BDZ) receptors in selected brain areas. Adult offspring of rats stressed during the last week of pregnancy exhibited higher levels of anxiety than control rats. The anxiogenic behavior found at the elevated plus maze (EPM) has been related to the reduced levels of BDZ receptor levels in specific brain areas. Adult offspring of rats stressed during pregnancy exhibited a decrease in the number of BDZ receptors binding sites in the central amygdaloid nucleus (Ce), CA1, CA3, and the dentate gyrus regions of the hippocampus when compared to controls. Regarding the adoption procedure, control pups raised by a foster gestationally stressed mother showed similar levels of anxiety as stressed groups. Stressed offspring raised by a foster control mother showed reduced anxiety levels compared to that of the control groups. Adoption per se showed no difference in time spent, neither in the open arms of the plus maze nor in BDZ receptor levels, when compared to the corresponding control and stressed groups. Stressed offspring raised by a foster control mother reverted BDZ receptor levels to control values. However, control pups raised by a gestationally stressed foster mother showed similar values compared to the control offspring in hippocampus, in spite of showing an anxiogenic behavior in the EPM. We found a significant increase of Ce BDZ receptor levels in control offspring raised by a foster stressed mother that could be explained as a compensatory effect to a GABA receptor desensitization. In summary, the behavioral outcome of the adult offspring is vulnerable both to the stress experience during the late prenatal period as well as to possible variations in care during lactation by mothers subjected to chronic stress during gestation. There seems to be a direct correlation between anxiety state and BDZ receptor levels in the adult offspring raised by their biological mothers. However, the mechanism of BDZ regulation leading to an anxious behavior might be different if the insult is received only postnatally as opposed to both pre and postnatally.