title: Anxiolytic effects of hippocampal neurosteroids in normal and neuropathic rats with spared nerve injury.
abstract: Neurosteroids are synthesized in the nervous system from cholesterol or steroidal precursors imported from peripheral sources. These compounds are important allosteric modulators of GABAAreceptors, which play a vital role in modulating hippocampal functions. Chronic pain is accompanied by increased neurosteroid production in the spinal cord and thalamus. We hypothesize that hippocampal neurosteroids participate in pain or pain-associated emotions, which we tested with high-performance liquid chromatography/tandem mass spectrometry and pharmacological behavioral tests. We observed increased levels of hippocampal neurosteroids (pregnenolone, progesterone, deoxycorticosterone, and allopregnanolone) in rats with chronic neuropathic pain (28 days after spared nerve injury). Meanwhile, the expression of the translocator protein, the upstream steroidogenesis rate-limiting enzyme, increased in the ventral but not dorsal hippocampus of neuropathic rats. In both naïve and neuropathic rats, in vivo stereotaxic microinjection of PK 11195, the translocator protein inhibitor, into the ventral hippocampus exacerbated anxiety-like behaviors. These results indicate anxiolytic effects of hippocampal neurosteroids in both normal and neuropathic rats. Neurosteroids could be considered as agents for treatment of general and pain-related anxiety disorders.
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, China.|Department of Pathology, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Institute of Systems Biomedicine, Peking University, Beijing, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, China.
authors.forename: Meng-Meng
authors.initials: MM
authors.lastname: Zhou
authors.affiliation: Department of Pharmacy, Bethune International Peace Hospital, Shijiazhuang, China.
authors.forename: Honghai
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Pharmacy, Bethune International Peace Hospital, Shijiazhuang, China.
authors.forename: Yanning
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Department of New Drug Evaluation, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Li
authors.affiliation: Institute of Systems Biomedicine, Peking University, Beijing, China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, Key Laboratory of Molecular Cardiovascular Sciences of the Ministry of Education, Peking University, Beijing, China.
authors.forename: Lemin
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Cai
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, China.
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Liao
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, China.
authors.forename: Feng-Yu
authors.initials: FY
authors.lastname: Liu
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yi
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, China.|Key Laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, China.|Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: You
authors.initials: Y
authors.lastname: Wan
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000032:analysis / Q000378:metabolism*; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D009437:Neuralgia / Q000378:metabolism* / Q000517:prevention & control / Q000523:psychology*; D018377:Neurotransmitter Agents / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D014151:Anti-Anxiety Agents; D018377:Neurotransmitter Agents
keywords: anxiety; hippocampus; neurosteroids; pain; spared nerve injury; translocator protein