Neuroplastic changes following repeated exposure to cocaine during adolescence: Focus on the glutamatergic system

Objective : To investigate changes in glutamate receptors expression and phosphorylation following repeated exposure to cocaine during adolescence. Methods : We therefore treated male rats from post-natal day (PND) 28 to PND 42 with saline or cocaine (20 mg/kg). Animals were sacrificed 3 days (PND 45) after the end of treatment or at adulthood (PND 90) and the brain regions of interest (prefrontal cortex and nucleus accumbens) were removed. Analyses were carried out by Western blots. Results : No major changes were found in the phosphorylation or expression of the main subunits of NMDA receptors in the prefrontal cortex of PND 45-old rats with only a slight reduction in the major AMPA subunit, i.e. GluR1 ; conversely, in nucleus accumbens, we found increased phosphorylation, but not expression, of NR1, NR2B and GluR1. At adulthood, we primarily found a significant reduction in GluR1 expression and phosphorylation in the prefrontal cortex with no major changes in the nucleus accumbens. Additionally, when we challenged the animals with an acute stress to evaluate whether exposure to cocaine during adolescence had altered the response of the glutamatergic system to the stress itself, we found a dysregulated response in the phosphorylation of the main glutamatergic subunits, i.e. the NR-1 NMDA subunit and the GluR-1 AMPA subunit. Conclusion: Our results suggest 1) an early activation of the glutamate system in nucleus accumbens ; 2) a persistent effect of the exposure to cocaine during adolescence on GluR-1 subunit, which persists into adulthood 3) a dynamic role of glutamatergic receptors following adolescential exposure to cocaine which is not limited to changes at the steady state level of these receptors.