Prenatal stress in rats : effects of cytogenesis, cocaine-induced place preference and dopamine

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The present study examined the effects of prenatal stress on the cytogenesis in the subventricular zone that may implicate in the altered effectiveness of rewarding cocaine in the offspring rats.During five embryonic days (E13 to E17), pregnant dams were restrained for 45 min, three times a day, in the Bolman cages exposed to two bright (150w) lights. For cell-proliferation study, dams were injected with a cell-proliferation marker 5-bromo-2' deoxyuridine (BrdU ; 50mg/kg, i.p.), following each stress session on days of E13, E15, and E17. Pups were then perfused on postnatal day 7 or 10 and BrdU-positive cells were counted in the subgranular zone of the hippocamus and the subventricular zone, respectively. To investigate rewarding effectiveness of cocaine in the offspring rats, ten-week-old offsprings were trained with cocaine (0, 2.5, 5.0, 10.0 mg/kg, i.p.) to establish place preference. Additionally, cocaine-enhanced extracellular dopamine concentration in the nucleus accumbens, was examined by using in-vivo microdialysis and high-performance liquid chromatography.The prenatally stressed offsprings showed (1) remarkably fewer BrdU positive cells not only in the subgranular zone but also in the subventricular zone and (2) Higher rewarding effectiveness of cocaine revealed in conditioned place preference test than that in control offsprings. But, prenatal stress did not affect the cocaine-increased extracellular dopamine in the nucleus accumbens.The results indicate that prenatal stress, particularly applied during the later period of pregnancy, may lead to a reduction in cell proliferation of the subventricular zone in the fetus and a hypersensitization to the rewarding cocaine. The later alteration seems not due to the hyperreaction of accumbal dopamine to the cocaine.