ИСТИНА

The role of damaging factors in prenatal period as basis of drug addiction in offspring is of great interest. Our investigation aims to study the effects and possible mechanisms of prenatal hypoxia (PSH) on the vulnerability to nicotine addiction in adult 3-months old rats. In PSH group, we have revealed an increased tendency to nicotine consumption in behavioral tests. In an attempt to find out an explanation for the addictive behavior of PSH rats, we previously revealed increased amount of phosphorylated at the 34th threonine residue DARPP-32 protein (known as the relay for dopamine and glutamate signaling) in the nucleus accumbens (NAc). The observed proportion of DARPP-32/phosphoDARPP-32 could not be explained by alterations in the amount of dopamine and its receptors in the NAc. As a protentional, explanation, we consider the decreasing of glutamatergic stimulation of NAc neurons from projections of ventral hippocampus, in which we found decreased glucocorticoid-dependent transcription of genes of glutamate metabolism. Meanwhile, another potential explanation might be increasing expression of the chrna7 gene, which codes nicotinic acetylcholine receptors of type 7 localized on presynapses of glutamatergic projections to such structures of the mesocortical pathway, as the prefrontal cortex (PFC) and ventral tegmental area (VTA), in which an increase in VGluT2-positive glutamatergic terminals were also found. Thus, the accelerated development of nicotine addiction in experimental rats is probably associated with PSH-related phenotype of acetylcholine and glutamatergic systems, namely with increased glutamatergic stimulation of VTA and PFC neurons and decreased stimulation of NAc from hippocampal glutamatergic projections.