30 Years of Dynorphins – New Insights on Their Functions in Neuropsychiatric Diseases

摘要: Since the first description of their opioid properties three decades ago, dynorphins have increasingly been thought to play a regulatory role in numerous functional pathways brain. Dynorphins are members peptide family and preferentially bind kappa receptors. In line with localization hippocampus, amygdala, hypothalamus, striatum spinal cord, functions related learning memory, emotional control, stress response pain. Pathophysiological mechanisms that may involve dynorphins/kappa receptors include epilepsy, addiction, depression schizophrenia. Most these were proposed 1980s 1990s following histochemical, pharmacological electrophysiological experiments using receptor-specific or general receptor agonists antagonists animal models. However, at time, we had little information on relevance endogenous dynorphins. This was mainly due complexity system. Besides actions peptides from all classical precursors (proenkephalin, prodynorphin, proopiomelanocortin) (delta, mu kappa), also shown exert non-opioid effects through direct NMDA Moreover, discrepancies between distribution binding sites dynorphin immunoreactivity contributed difficulties interpretation. recent years, generation prodynorphin- receptor-deficient mice has provided tools investigate open questions network dynorphins. This article examines physiological, pathophysiological implications light new insights part obtained genetically modified animals.