title: Translocator protein mediates the anxiolytic and antidepressant effects of midazolam.
abstract: The translocator protein (18 kDa) (TSPO) plays an important role in stress-related disorders, such as anxiety, depression and post-traumatic stress disorder (PTSD), caused by neurosteroids (e.g. allopregnanolone). The present study sought to evaluate the significance of TSPO in anxiolytic and antidepressant effects induced by midazolam. The animals were administrated midazolam (0.25, 0.5 and 1 mg/kg, i.p.) and subjected to behavioral tests, including Vogel-type conflict test, elevated plus-maze test, forced swimming test. Midazolam produced anxiolytic- and antidepressant-like effects Vogel-type conflict test (1 mg/kg, i.p.), elevated plus-maze test (0.5 and 1 mg/kg, i.p.), and forced swimming test (0.5 and 1 mg/kg, i.p.). These effects of Midazolam were totally blocked by the TSPO antagonist PK11195 (3 mg/kg, i.p.). To evaluate the role of allopregnanolone in the anxiolytic- and antidepressant-like effects of midazolam, the animals were decapitated at the end of the behavioral tests. The allopregnanolone levels of the prefrontal cortex and hippocampus were measured by enzyme-linked immunosorbent assay (ELISA). The allopregnanolone level of the prefrontal cortex and hippocampus was increased by midazolam (0.5, 1 mg/kg, i.p.) and the increase was reversed by PK11195 (3 mg/kg, i.p.). Overall, the results indicated that the anxiolytic- and antidepressant-like effects of midazolam were mediated by TSPO, via stimulation of allopregnanolone biosynthesis.
authors.affiliation: Pharmaceutical Department of the First Affiliated Hospital of Guangdong Pharmaceutical University, Clinical Pharmacy Department of Guangdong Pharmaceutical University, Guangzhou 510080, PR China.
authors.forename: Zhi-Kun
authors.initials: ZK
authors.lastname: Qiu
authors.affiliation: Department of Anesthesiology, The Centre Hospital of Taian, Taian 271000, PR China.
authors.forename: Ming-Sheng
authors.initials: MS
authors.lastname: Li
authors.affiliation: Department of Endocrinology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, PR China. Electronic address: doctor_carriehe@163.com.
authors.forename: Jia-Li
authors.initials: JL
authors.lastname: He
authors.affiliation: Pharmacy Department of General Hospital of Chinese People's Armed Police Forces, Beijing 100039, PR China.
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Neurosurgery Department of the Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, PR China.
authors.forename: Guan-Hua
authors.initials: GH
authors.lastname: Zhang
authors.affiliation: Pharmaceutical Department of the First Affiliated Hospital of Guangdong Pharmaceutical University, Clinical Pharmacy Department of Guangdong Pharmaceutical University, Guangzhou 510080, PR China.
authors.forename: Sha
authors.initials: S
authors.lastname: Lai
authors.affiliation: Pharmaceutical Department of the First Affiliated Hospital of Guangdong Pharmaceutical University, Clinical Pharmacy Department of Guangdong Pharmaceutical University, Guangzhou 510080, PR China.
authors.forename: Jian-Chun
authors.initials: JC
authors.lastname: Ma
authors.affiliation: Pharmaceutical Department of the First Affiliated Hospital of Guangdong Pharmaceutical University, Clinical Pharmacy Department of Guangdong Pharmaceutical University, Guangzhou 510080, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Pharmaceutical Department of the First Affiliated Hospital of Guangdong Pharmaceutical University, Clinical Pharmacy Department of Guangdong Pharmaceutical University, Guangzhou 510080, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Pharmaceutical Department of the First Affiliated Hospital of Guangdong Pharmaceutical University, Clinical Pharmacy Department of Guangdong Pharmaceutical University, Guangzhou 510080, PR China.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Wu
authors.affiliation: Pharmaceutical Department of the First Affiliated Hospital of Guangdong Pharmaceutical University, Clinical Pharmacy Department of Guangdong Pharmaceutical University, Guangzhou 510080, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Pharmaceutical Department of the First Affiliated Hospital of Guangdong Pharmaceutical University, Clinical Pharmacy Department of Guangdong Pharmaceutical University, Guangzhou 510080, PR China.
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Shen
authors.affiliation: Pharmaceutical Department of the First Affiliated Hospital of Guangdong Pharmaceutical University, Clinical Pharmacy Department of Guangdong Pharmaceutical University, Guangzhou 510080, PR China. Electronic address: cjslym@163.com.
authors.forename: Ji-Sheng
authors.initials: JS
authors.lastname: Chen
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002352:Carrier Proteins / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008874:Midazolam / Q000008:administration & dosage / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011280:Pregnanolone / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology*
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D002352:Carrier Proteins; D007546:Isoquinolines; D011963:Receptors, GABA-A; C069997:Tspo protein, rat; D011280:Pregnanolone; D008874:Midazolam; C037850:PK 11195
keywords: Allopregnanolone; Antidepressant; Anxiolytic; Midazolam; TSPO