title: Injection of Toll-like receptor 4 siRNA into the ventrolateral periaqueductal gray attenuates withdrawal syndrome in morphine-dependent rats.
abstract: We assessed the role of the Toll-like receptor 4 (TLR4) gene in the ventrolateral periaqueductal gray (vlPAG) region of morphine-dependent rats on attenuating withdrawal syndrome, and regulating glutamic acid decarboxylase (GAD67), glutamic acid (Glu), and gamma-aminobutyric acid (GABA). After siRNA-mediated downregulation of TLR4, changes were observed in withdrawal behavior and downstream signaling molecules. Rats were injected into the vlPAG with TLR4 siRNA, followed by intraperitoneal injection of morphine for 5 consecutive days, and then naloxone, and the behavioral indices of morphine withdrawal were observed. 'Wet-dog' shakes, teeth chattering, and the total scores of withdrawal reactions were reduced. TLR4 expression and Glu levels were reduced, whereas GAD67 and GABA levels were increased. Overall, these findings indicate that modifying TLR4 gene expression in the vlPAG stimulates expression of the downstream signaling molecule, GAD67, which decreases Glu levels and increases GABA levels. This mechanism may explain the inhibition of withdrawal syndrome in morphine-dependent rats.
authors.forename: Q F
authors.initials: QF
authors.lastname: Liu
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: Y Q
authors.initials: YQ
authors.lastname: Guo
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: Z D
authors.initials: ZD
authors.lastname: Mou
authors.affiliation: Department of Pathogenic Biology, Chengdu Medical College, Chengdu 610083, China - Email: joneke55@163.com.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, China - Email: du_guizhi@yahoo.com.
authors.forename: G Z
authors.initials: GZ
authors.lastname: Du
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005968:Glutamate Decarboxylase / Q000096:biosynthesis*; D008297:Male; D009021:Morphine Dependence / Q000378:metabolism*; D010487:Periaqueductal Gray / Q000378:metabolism*; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis*
chemical_list: D034741:RNA, Small Interfering; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1