Multifunctional aspects of allopregnanolone in stress and related disorders

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• 作者：Anjana Bali ; Amteshwar Singh Jaggi
• 关键词：HPA ; Hypothalamus-pituitary- adrenal axis ; BDNF ; Brain-derived neurotrophic factor ; TSST ; Trier Social Stress test ; SBBS ; Steroidogenic stimulant ; CRF ; Corticotropin releasing factor ; mPFC ; median prefrontal cortex ; PBR ; Peripheral benzodiazepine receptors ; TSPO ; Translocator protein ; PVN ; Paraventricular nucleus ; sEPSCs ; Spontaneous excitatory postsynaptic current ; NKCC1 ; Na+-K+-Cl- co-transporter ; 3伪-HSD ; 3伪-hydroxysteroid dehydrogenase ; AlloP ; Allopregnanolone ; NMDA ; N-methyl-D-aspartate ; N
• 刊名：Progress in Neuro-Psychopharmacology and Biological Psychiatry
• 出版年：3 January, 2014
• 年：2014
• 卷：48
• 期：Complete
• 页码：64-78
• 全文大小：919 K

文摘

Allopregnanolone (3伪-hydroxy-5伪-pregnan-20-one) is a major cholesterol-derived neurosteroid in the central nervous system and is synthesized from progesterone by steroidogenic enzymes, 5伪-reductase (the rate-limiting enzyme) and 3伪-hydroxysteroid dehydrogenase. The pathophysiological role of allopregnanolone in neuropsychiatric disorders has been highlighted in several investigations. The changes in neuroactive steroid levels are detected in stress and stress-related disorders including anxiety, panic and depression. The changes in allopregnanolone in response to acute stressor tend to restore the homeostasis by dampening the hyper-activated HPA axis. However, long standing stressors leading to development of neuropsychiatric disorders including depression and anxiety are associated with decrease in the allopregnanolone levels. GABA_A receptor complex has been considered as the primary target of allopregnanolone and majority of its inhibitory actions are mediated through GABA potentiation or direct activation of GABA currents. The role of progesterone receptors in producing the late actions of allopregnanolone particularly in lordosis facilitation has also been described. Moreover, recent studies have also described the involvement of other multiple targets including brain-derived neurotrophic factor (BDNF), glutamate, dopamine, opioids, oxytocin, and calcium channels. The present review discusses the various aspects of allopregnanolone in stress and stress-related disorders including anxiety, depression and panic.