ИСТИНА

The question of the role of prenatal maternal stress as molecular and cellular basis of addiction in offspring is of great interest. This investigation aims to study the effect of prenatal hypoxia (PH) on the vulnerability to nicotine consumption in 3-month-old rats, and the assessment of the severity of withdrawal after the chronic treatment with nicotine. To simulate prenatal hypoxia, we placed female rats on days 14-16 of pregnancy in a flow-type pressure chamber for 3 hours. The pressure at a peak value was 180 mmHg. In the PH rats, we revealed an increased tendency to nicotine selfadministration in two-bottle choice paradigm in comparison with the control group. For assessment of withdrawal, control and PH rats were subcutaneously implanted with osmotic mini-pumps filled with nicotine tartrate solution or saline. After two weeks of «forced consumption», the effectiveness of the development of nicotine dependence was assessed in the conditioned place aversion test with mecamylamine. It is shown that the mecamylamine-precipitated withdrawal aversion in the compartment associated with its administration is higher in PH group than in the control group. When studying the alterations of dopamine system in adult rats who exposed to PH, we find an increase in the proportion of DARPP-32 phosphorylated at Thr34 in relation to the total DARPP-32 in the nucleus accumbens against the background of the absence of any changes in the amount of dopamine in striatum and midbrain and DRD1 in the striatum. In addition, we discovered a decrease in the number of VGluT2-positive terminals colocalized with DARPP-32 in the nucleus accumbens of PH rats, which might indicate that it is the disturbances of glutamate stimulation of striatal neurons in the nucleus accumbens that predetermines the tendency to nicotine addiction and the severity of withdrawal symptoms due to prenatal hypoxia. Supported by RFBR grant № 19-315-90003.