A single dose of ketamine produces antidepressant-like effects in rats only when the brain's own opioid system is active in the medial prefrontal cortex (mPFC). Blocking opioid receptors with naltrexone—either throughout the body or directly in the mPFC—eliminates ketamine's behavioral effects. Ketamine rapidly increases levels of the opioid β-endorphin and expression of the μ-opioid receptor gene in the mPFC, and boosts production of β-endorphin's precursor in the hypothalamus. Neutralizing β-endorphin in the mPFC with a specific antibody also abolishes ketamine's behavioral and molecular effects, demonstrating that β-endorphin and opioid receptor activation in the mPFC are necessary for ketamine's antidepressant-like actions.
A single dose of ketamine's antidepressant-like effects in rats require the brain's own opioid system, specifically β-endorphin and mu-opioid receptors in the medial prefrontal cortex (mPFC). Blocking opioid receptors with naltrexone, either throughout the body or directly in the mPFC, prevented ketamine's behavioral effects and associated molecular changes. Ketamine rapidly increased β-endorphin levels and mu-opioid receptor gene expression in the mPFC, as well as the gene for β-endorphin's precursor in the hypothalamus. Neutralizing β-endorphin in the mPFC with a specific antibody before ketamine also abolished both behavioral and molecular effects, demonstrating that activation of mPFC opioid receptors is necessary for ketamine's antidepressant-like actions.
A systematic review and meta-analysis of seven randomized controlled trials (479 participants) found that mindfulness-based cognitive therapy (MBCT) reduced suicidal ideation and depressive symptoms more than treatment as usual in patients with current depression. The effect on suicidal ideation was modest (standard mean difference -0.33) and on depression was larger (-0.96). The authors conclude MBCT is an effective intervention for reducing both outcomes in depressed patients.