title: Phosphodiesterase 10A inhibition attenuates sleep deprivation-induced deficits in long-term fear memory.
abstract: Sleep, particularly rapid eye movement (REM) sleep, is implicated in the consolidation of emotional memories. In the present study, we investigated the protective effects of a phosphodiesterase 10A (PDE10A) inhibitor MP-10 on deficits in long-term fear memory induced by REM sleep deprivation (REM-SD). REM-SD caused deficits in long-term fear memory, however, MP-10 administration ameliorated the deleterious effects of REM-SD on long term fear memory. Brain-derived neurotropic factor (BDNF) and phosphorylated cAMP response element-binding protein (pCREB) were altered in specific brain regions associated with learning and memory in REM-SD rats. Accordingly, REM-SD caused a significant decrease of pCREB in hippocampus and striatum and a significant decrease of BDNF in the hippocampus, striatum and amygdala, however, MP-10 reversed the effects of REM-SD in a dose-dependent manner. Our findings suggest that REM-SD disrupts the consolidation of long-term fear memory and that administration of MP-10 protects the REM-SD-induced deficits in fear memory, which may be due to the MP-10-induced expression of BDNF in the hippocampus, striatum and amygdala, and phosphorylation of CREB in the hippocampus and striatum.
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuropsychiatric Disorders & Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, 199 Ren'ai Road, Suzhou, Jiangsu 215123, China; College of Pharmaceutical Sciences, Suzhou Health College, 28 Kehua Road, Suzhou, Jiangsu 215009, China.
authors.forename: Lengqiu
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Rehabilitation Medicine, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road,Qingdao, Shandong 266003, China.
authors.forename: Zhuangli
authors.initials: Z
authors.lastname: Guo
authors.affiliation: College of Pharmaceutical Sciences, Suzhou Health College, 28 Kehua Road, Suzhou, Jiangsu 215009, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Luo
authors.affiliation: College of Pharmaceutical Sciences, Suzhou Health College, 28 Kehua Road, Suzhou, Jiangsu 215009, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liang
authors.affiliation: College of Pharmaceutical Sciences, Suzhou Health College, 28 Kehua Road, Suzhou, Jiangsu 215009, China.
authors.forename: Shui
authors.initials: S
authors.lastname: Yang
authors.affiliation: College of Pharmaceutical Sciences, Suzhou Health College, 28 Kehua Road, Suzhou, Jiangsu 215009, China.
authors.forename: Haigang
authors.initials: H
authors.lastname: Ren
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuropsychiatric Disorders & Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, 199 Ren'ai Road, Suzhou, Jiangsu 215123, China. Electronic address: wanggh@suda.edu.cn.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuropsychiatric Disorders & Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, 199 Ren'ai Road, Suzhou, Jiangsu 215123, China. Electronic address: zhenxuechu@suda.edu.cn.
authors.forename: Xuechu
authors.initials: X
authors.lastname: Zhen
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005239:Fear / Q000187:drug effects*; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology; D057567:Memory, Long-Term / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D010766:Phosphorylation; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects; D012892:Sleep Deprivation / Q000150:complications / Q000523:psychology*; D012895:Sleep, REM
chemical_list: C545121:2-((4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)phenoxy)methyl)quinoline; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D010726:Phosphodiesterase Inhibitors; D011720:Pyrazoles; D011804:Quinolines; C119843:PDE10A protein, human; D010727:Phosphoric Diester Hydrolases
keywords: Fear memory; Phosphodiesterase-10; REM sleep deprivation