Chronic exposure to corticosterone enhances the neuroinflammatory and neurotoxic responses to methamphetamine

摘要: Up-regulation of proinflammatory cytokines and chemokines in brain ("neuroinflammation") accompanies neurological disease neurotoxicity. Previously, we documented a striatal neuroinflammatory response to acute administration neurotoxic dose methamphetamine (METH), i.e. one associated with evidence dopaminergic terminal damage activation microglia astroglia. When used minocycline suppress METH-induced neuroinflammation, indices neurotoxicity were not affected, but suppression neuroinflammation was incomplete. Here, administered the classic anti-inflammatory glucocorticoid, corticosterone (CORT), an attempt completely METH-related neuroinflammation. METH alone caused large increases cytokine/chemokine mRNA subsequent astrocytic hypertrophy, microglial activation, nerve damage. Pre-treatment mice CORT failed prevent responses METH. Surprisingly, when pre-treated chronic drinking water, enhanced observed, effect that accompanied by astrogliosis Chronic pre-treatment also sensitized frontal cortex hippocampus mount Because levels are high physiological stress, our data suggest therapy or sustained stress may sensitize