A therapeutic combination of metyrapone and oxazepam increases brain levels of GABA-active neurosteroids and decreases cocaine self-administration in male rats

摘要: In rodents, the behavioral and neurochemical effects resulting from pharmacological blockade of hypothalamo-pituitary-adrenal (HPA) axis are unclear. Metyrapone, a corticosterone synthesis inhibitor, has been demonstrated to reduce cocaine-related behaviors, especially in low-dose combination with oxazepam, benzodiazepine. Although this therapy (MET/OX) also reduces drug-taking drug-seeking behaviors both rodents cocaine-dependent humans, these not correlated plasma glucocorticoid levels. brief report, we present data demonstrating that MET/OX enhances brain levels GABA-active steroid metabolites, tetrahydrodeoxycorticosterone (THDOC) allopregnanolone. Male rats, trained self-administer cocaine or received yoked-saline infusions, were pretreated MET/OX, at doses reduced cocaine-motivated responding, vehicle. Allopregnanolone THDOC measured using liquid chromatography-mass spectroscopy (LC-MS/MS) prefrontal cortex amygdala brains rats. enhanced following pretreatment regions, regardless self-administration experience. However, allopregnanolone was selectively rats self-administered cocaine, but group. Thus, increased neurosteroid content regions important for drug addiction. These neurosteroids have shown may contribute therapy.