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Anxiolytic effects of hippocampal neurosteroids in normal and neuropathic rats with spared nerve injury
Author(s) -
Zhang Meng,
Liu Jia,
Zhou MengMeng,
Wu Honghai,
Hou Yanning,
Li YunFeng,
Yin Yuxin,
Zheng Lemin,
Cai Jie,
Liao FeiFei,
Liu FengYu,
Yi Ming,
Wan You
Publication year - 2017
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13965
Subject(s) - neuroactive steroid , anxiolytic , hippocampal formation , neuroscience , medicine , anesthesia , nerve injury , neuropathic pain , psychology , gabaa receptor , receptor
Abstract Neurosteroids are synthesized in the nervous system from cholesterol or steroidal precursors imported from peripheral sources. These compounds are important allosteric modulators of GABA A receptors, 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.