CONICET | Buscador de Institutos y Recursos Humanos

Repeated restraint stress during the last week of pregnacy produces offspring that show severe anomalies in neural development and brain morphology that persists into adulthood particularly in dopaminergic neurotransmission. We have previously shown that prenatal stress (PS) increases D2-type dopamine (DA) receptor levels with a concomitant reduction in DA release. In this study, we show that PS increased D2 receptors both in the left and right sides of Nucleus Accumbens Core (NacC), but the left-right asymmetry observed in the control group, was selectively lost in adult rats exposed to PS. The transcription factors (TFs) Nurr1 and Pitx3 are expressed at critical moments of DA neurons differentiation and has been related to the modulation of tyrosine hydroxylase (TH) expression. Employing an immunocytochemical approach, we studied the expression levels of both TFs and TH in brain slices of PS rats during postnatal development. Our results show that the expression of both Nurr1 and Pitx3 increased in PS offspring in the Ventral Tegmental Area (VTA) at PND 7 and PND 60, whereas no changes were observed in Substantia Nigra (SN) areas. TH expression was reduced at PND 7 in VTA and recovered to control values at PND 28 and 60. The increase of the specific DA TFs and TH expression might be a compensatory mechanism to counteract the reduction in DA levels observed, which in turn might be up-regulating D2 DA receptors. Since DA release is still impaired at adult ages we speculate that other steps in the DA synthesis and storage metabolism might also be altered. The area selectivity of the increase in the TFs and TH towards VTA and the mesolimbic pathway indicates that an insult received during the prenatal period will exert mainly motivational, emotional and reward behaviour impairments in the adult life.