NFκB1 and NFκB2 gene expression in the prefrontal cortex and hippocampus of early life stressed mice exposed to cocaine-induced conditioned place preference during adolescence

Neuro-immune pathways contribute to the onset and maintenance of cocaine-seeking behaviors, particularly through activation of NFκB signaling in the brain. However, the molecular mechanisms of this relationship are still not completely understood, especially considering the effects of early life stress, a major risk factor to cocaine addiction. The goal of this study was to investigate NFκB1 and NFκB2 gene expression in the prefrontal cortex (PFC) and hippocampus of mice exposed to early life stress and cocaine-induced conditioned place preference (CPP) within adolescence. Male BALB/c mice were randomly assigned to one of four groups: animal facility reared (AFR) with or without CPP training; maternal separation (MS) with our without CPP training. The MS animals were subjected to daily 3-h maternal separation from postnatal day (PND) 2 to 15. CPP was performed following three sequential phases: habituation (PND 34), conditioning (PND 35 to PND 44) and post-conditioning test (PND 45). Gene expression was determined by qPCR. NFκB1 mRNA levels were decreased in the PFC of animals exposed to CPP compared to drug-naïve animals, while no difference was detected regarding rearing conditions. NFκB2 expression was upregulated in the PFC of animals exposed to CPP when compared to drug-naïve animals, particularly in animals exposed to MS with higher CPP scores. No significant effects were detected in the hippocampus. Cortical NFκB2 up-regulation may be involved with the enhanced motivational salience for cocaine-paired cues observed in animals exposed to MS during adolescence.