Previous Ketamine Produces an Enduring Blockade of Neurochemical and Behavioral Effects of Uncontrollable Stress

摘要: Recent interest in the antidepressant and anti-stress effects of subanesthetic doses ketamine, an NMDA receptor antagonist, has identified mechanisms whereby ketamine reverses effect stress, but little is known regarding prophylactic might have on future stressors. Here we investigate against neurochemical behavioral changes that follow inescapable, uncontrollable tail shocks (ISs) Sprague Dawley rats. IS induces increased anxiety, which dependent activation serotonergic (5-HT) dorsal raphe nucleus (DRN) neurons project to basolateral amygdala (BLA). Ketamine (10 mg/kg, i.p.) administered 2 h, 1 week, or weeks before prevented extracellular levels 5-HT BLA typically produced by IS. In addition, at these time points blocked decreased juvenile social investigation Microinjection into prelimbic (PL) region medial prefrontal cortex duplicated systemic and, conversely, were pharmacological inhibition PL. Although does not activate DRN-projecting from PL, did so after suggesting a result altered functioning this projection. SIGNIFICANCE STATEMENT The reported data show given up stressor, blunts stressor. study also advances understanding involved suggests acts sensitize inhibit DRN.