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Prenatal antiandrogen flutamide affects mesocorticolimbic dopaminergic system development in rats
PALLARÉS ME; ADROVER E; IMSEM M; BAIER CJ; ANTONELLI MC
Congreso; 43rd Annual Meeting of the Society of Neuroscience; 2013
We have previously shown that prenatal stress (PS) increases D2-type dopamine (DA) receptor (D2R) levels in frontal cortex, nucleus accumbens (NAcc) core and hippocampus. In this study, we found that prenatal stress increased D2R both in the left and right sides of NAcc core, but the left-right asymmetry observed in the control group, was selectively lost in adult rats exposed to prenatal stress. In addition, we measured the levels of DA in brain by microdialysis following amphetamine injections to freely moving rats. We observed a decrease of amphetamine stimulated dialysate in prefrontal cortex of prenatally stressed rats of 8 weeks old as compared with controls. Employing an inmunocytochemistry approach, we studied the expression levels of two transcription factors Nurr1 and Pitx3 which are expressed at critical moments of DA neurons differentiation. We found a ubiquitous distribution of Nurr-1 in cerebral cortex, hippocampus, thalamus, amygdala and midbrain whereas Pitx3 remains restricted to the mesencephalic DA system such as substancia nigra (SN) and ventral tegmental area (VTA). Our results show that the expression of both Nurr-1 and Pitx3 increased in prenatally stressed adult offspring in the VTA area, whereas no changes were observed in SN areas. Taken together these results show that several components of the limbic dopaminergic system are disregulated as a consequence of the prenatal insult. Loss of asymmetries of the D2 receptors in NacC can lead to long term behavioral and cognitive impairments. The increase of the specific dopaminergic transcription factors might be a compensatory mechanism to counteract the reduction in dopamine levels observed in PFC, which in turn might be upregulating D2 dopaminergic receptors.