Increases in Pro-inflammatory Cytokines in the Ventral Striatum Following Frequent Morphine Exposure Impose New Setpoints in the Expression of Biologically-Relevant Genes to Addiction and Neuroinflammation in Rats

Background: The ventral striatum is an integrated drug reward and addiction center. Objectives: We aimed to examine changes in pro-inflammatory cytokines subsequent the expression of biologically-relevant genes neuroinflammation response frequent morphine exposure. Methods: Sixteen male Wistar rats were divided into two experimental groups, a control, morphine-treated group, receiving eight days twice-daily injections either saline or sulfate (10 mg/kg). Results: results revealed that treatment increased both gene protein levels cytokines, including tumor necrosis factor α, interleukin 1-β, 6 striatum. Frequent also induced significant upregulations mRNA mu-opioid receptor, dopamine D1 receptor (Drd1), Fos, nuclear factor- kappa B, pre-miRNAs including, mir-124, mir-133b, mir-339, mir-365, Let-7c1 On contrary, injection significantly downregulated toll-like 4, cannabinoid CB1 CB2 receptors, Drd2, Il1r, Il6r, tnfr, kinase Cγ, calcium/calmodulin-dependent IIα, nitric oxide synthase, cAMP-response element-binding as well p38 Jnk3 MAP kinases However, no group differences detected Erk1 mir-219 Conclusions: It can be concluded dysregulations and, subsequently, downstream signaling pathways impair physiological functions following chronic exposure, affecting tolerance dependence.