ИСТИНА

Prenatal pathologies like fetal hypoxia or prenatal stress are increasingly recognized contributors to later-life neuropsychiatric diseases. These pathologies often co-occur, making it challenging to distinguish their individual effects. To address this, we modeled prenatal severe hypoxia (PSH) associated with maternal stress, or prenatal intrauterine ischemia (PII). Both adult PSH and PII rats showed elevated HIF1α levels in the hippocampus (HPC), but only PSH rats exhibited an impaired circadian glucocorticoid rhythm, demonstrating the suitability of both models for the research objectives. Comparing the two models, hypoxia was found insignificant for the further development of nicotine addiction. Specifically, the PSH group was the only one to demonstrate behavioral signs of nicotine addiction in the conditioned place aversion test and the normalization of aberrant latency in the startle response test under nicotine administration. Increased levels of DARPP-32 phosphorylated at threonine 34 (pThr34DARPP-32) in the nucleus accumbens (NAc) of PSH rats, but not the PII group, suggested attenuated glutamatergic efferent signaling as a significant predisposing factor for PSH-associated nicotine addiction. Additionally, reduced α7 nAChR expression was observed in the prefrontal cortex(PFC) and HPC, key regions projecting glutamatergic signals to the NAc. Strong correlations between glucocorticoid receptor (GR) encoded by nr3c1 and α7 subunits of nAChR encoded by chrna7 were found in both structures. Thus, perturbations in the glucocorticoid neuroendocrine system, along with glucocorticoid-dependent gene expression of chrna7 associated with maternal stress response to hypoxia in the prenatal period, contribute to the development of nicotine addiction in adulthood. Supported by RSF Grant #22-75-00003.