title: GABAB receptors in the hippocampal dentate gyrus are involved in spatial learning and memory impairment in a rat model of vascular dementia.
abstract: The roles of γ-aminobutyric acid (GABA) and GABAB receptors of the hippocampal dentate gyrus (DG) in spatial learning and memory impairment were investigated in a rat model of vascular dementia (VaD) established by permanent bilateral carotid occlusion. The extracellular concentration of GABA in the DG was determined by in vivo microdialysis and HPLC, and spatial learning and memory were assessed by the Morris water maze (MWM) test. Next, the possible involvement of GABAB receptors in spatial learning and memory impairments of VaD rats was examined by microinjection of its antagonist into the DG region. In VaD group rats, the extracellular concentration of GABA in the DG was significantly increased, and during MWM test, the escape latency was increased in place navigation trial and the percentage of time spent in target quadrant and the number of platform crossings were decreased in spatial probe trial, compared with the sham group. In sham-operated rats, the extracellular concentrations of glutamate (Glu) and glycine (Gly) in the DG were significantly increased during place navigation trial of MWM test, and these responses were inhibited in VaD rats. Saclofen (an antagonist of GABAB receptor) significantly attenuated the spatial learning and memory impairment in VaD rats, and partly reversed the inhibitory effects of VaD in responses of Glu and Gly in the DG during MWM test. Our results suggest that GABA and GABAB receptors in the hippocampal DG are involved in spatial learning and memory impairment in VaD rats, in part by attenuating the responses of Glu and Gly during spatial learning.
authors.affiliation: Department of Physiology and Pathophysiology, Yanbian University College of Medicine and Cellular Function Research Center, Yanbian University, Yanji 133002, China; Department of Surgery, Yanbian University Hospital, Yanji 133000, China.
authors.forename: Guangxie
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, Yanbian University College of Medicine and Cellular Function Research Center, Yanbian University, Yanji 133002, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Physiology and Pathophysiology, Yanbian University College of Medicine and Cellular Function Research Center, Yanbian University, Yanji 133002, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Physiology, Jilin Medical University, Jilin 132013, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wan
authors.affiliation: Department of Physiology and Pathophysiology, Yanbian University College of Medicine and Cellular Function Research Center, Yanbian University, Yanji 133002, China.
authors.forename: Yingshun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, Yanbian University College of Medicine and Cellular Function Research Center, Yanbian University, Yanji 133002, China. Electronic address: hyjiang@ybu.edu.cn.
authors.forename: Haiying
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Physiology and Pathophysiology, Yanbian University College of Medicine and Cellular Function Research Center, Yanbian University, Yanji 133002, China. Electronic address: yqinghua@ybu.edu.cn.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Jin
mesh_terms: D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D015140:Dementia, Vascular / Q000150:complications* / Q000209:etiology; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D018756:GABA Antagonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology*; D017202:Myocardial Ischemia / Q000150:complications; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D018080:Receptors, GABA-B / Q000378:metabolism*; D065853:Spatial Learning / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018756:GABA Antagonists; D058786:GABA-B Receptor Agonists; D018080:Receptors, GABA-B; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; C080629:saclofen; D005998:Glycine
keywords: GABA; GABA(B) receptors; Hippocampal dentate gyrus; Rats; Spatial learning and memory; Vascular dementia