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Activation and blockade of serotonin6 receptors in the dorsal hippocampus enhance T maze and hole-board performance in a unilateral 6-hydroxydopamine rat model of Parkinson's disease.
Brain Res 2016; 1650:184-195BR

Abstract

The role of dorsal hippocampus (DH) serotonin6 (5-HT6) receptors in memory is unknown, particularly in memory impairment of Parkinson's disease. We tested here effects of activation and blockade of DH 5-HT6 receptors on working and hippocampus-dependent memories in rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. The lesion induced working and hippocampus-dependent memory impairments as measured by the T-maze rewarded alternation and hole-board tests, and decreased dopamine (DA) levels in the striatum, medial prefrontal cortex (mPFC), DH and amygdala. Intra-DH injection of 5-HT6 receptor agonist WAY208466 (1.5, 3 and 6µg/rat) did not change choice accuracy and the number of head-dippings when re-exposure to hole-board in sham-operated rats, while 5-HT6 receptor antagonist SB258585 (4µg/rat) increased choice accuracy and decreased the number of head-dippings. In the lesioned rats, both WAY208466 (3 and 6µg/rat) and SB258585 (2 and 4µg/rat) increased choice accuracy and decreased the number of head-dippings. Neurochemical results showed that intra-DH injection of WAY208466 or SB258585 produced significant effects on DA and noradrenaline (NA) levels in the mPFC (WAY208466: sham-operated, NA -44%; lesioned, DA 522%, NA -47%; SB258585: sham-operated, DA 72%, NA 85%; lesioned, DA -68%), DH (WAY208466: lesioned, DA 427%; SB258585: sham-operated, DA 119%, NA 206%) and amygdala (WAY208466: sham-operated, NA -28%; lesioned, DA 302%; SB258585: sham-operated, NA 183%); however, 5-HT levels in these brain regions were not changed. These findings suggest DA depletion plays a key role in working and hippocampus-dependent memory impairments, and 5-HT6 receptors in the DH are involved in the regulation of the memories.

Authors+Show Affiliations

Department of Clinical Medicine, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.Department of Clinical Medicine, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.Department of Rehabilitation Medicine, the Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China.Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.Department of Rehabilitation Medicine, the Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China.Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: zhangli1998@mail.xjtu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27616337

Citation

Liu, Kun Cheng, et al. "Activation and Blockade of Serotonin6 Receptors in the Dorsal Hippocampus Enhance T Maze and Hole-board Performance in a Unilateral 6-hydroxydopamine Rat Model of Parkinson's Disease." Brain Research, vol. 1650, 2016, pp. 184-195.
Liu KC, Li JY, Xie W, et al. Activation and blockade of serotonin6 receptors in the dorsal hippocampus enhance T maze and hole-board performance in a unilateral 6-hydroxydopamine rat model of Parkinson's disease. Brain Res. 2016;1650:184-195.
Liu, K. C., Li, J. Y., Xie, W., Li, L. B., Zhang, J., Du, C. X., ... Zhang, L. (2016). Activation and blockade of serotonin6 receptors in the dorsal hippocampus enhance T maze and hole-board performance in a unilateral 6-hydroxydopamine rat model of Parkinson's disease. Brain Research, 1650, pp. 184-195. doi:10.1016/j.brainres.2016.09.009.
Liu KC, et al. Activation and Blockade of Serotonin6 Receptors in the Dorsal Hippocampus Enhance T Maze and Hole-board Performance in a Unilateral 6-hydroxydopamine Rat Model of Parkinson's Disease. Brain Res. 2016 11 1;1650:184-195. PubMed PMID: 27616337.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation and blockade of serotonin6 receptors in the dorsal hippocampus enhance T maze and hole-board performance in a unilateral 6-hydroxydopamine rat model of Parkinson's disease. AU - Liu,Kun Cheng, AU - Li,Jun Yi, AU - Xie,Wen, AU - Li,Li Bo, AU - Zhang,Jin, AU - Du,Cheng Xue, AU - Zhang,Yu Ming, AU - Tan,Hui Hui, AU - Wang,Hui Sheng, AU - Zhang,Li, Y1 - 2016/09/08/ PY - 2016/05/08/received PY - 2016/08/28/revised PY - 2016/09/06/accepted PY - 2016/9/13/pubmed PY - 2017/8/22/medline PY - 2016/9/13/entrez KW - 5-HT(6) receptors KW - Dorsal hippocampus KW - Memory KW - Parkinson's disease KW - Rat SP - 184 EP - 195 JF - Brain research JO - Brain Res. VL - 1650 N2 - The role of dorsal hippocampus (DH) serotonin6 (5-HT6) receptors in memory is unknown, particularly in memory impairment of Parkinson's disease. We tested here effects of activation and blockade of DH 5-HT6 receptors on working and hippocampus-dependent memories in rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. The lesion induced working and hippocampus-dependent memory impairments as measured by the T-maze rewarded alternation and hole-board tests, and decreased dopamine (DA) levels in the striatum, medial prefrontal cortex (mPFC), DH and amygdala. Intra-DH injection of 5-HT6 receptor agonist WAY208466 (1.5, 3 and 6µg/rat) did not change choice accuracy and the number of head-dippings when re-exposure to hole-board in sham-operated rats, while 5-HT6 receptor antagonist SB258585 (4µg/rat) increased choice accuracy and decreased the number of head-dippings. In the lesioned rats, both WAY208466 (3 and 6µg/rat) and SB258585 (2 and 4µg/rat) increased choice accuracy and decreased the number of head-dippings. Neurochemical results showed that intra-DH injection of WAY208466 or SB258585 produced significant effects on DA and noradrenaline (NA) levels in the mPFC (WAY208466: sham-operated, NA -44%; lesioned, DA 522%, NA -47%; SB258585: sham-operated, DA 72%, NA 85%; lesioned, DA -68%), DH (WAY208466: lesioned, DA 427%; SB258585: sham-operated, DA 119%, NA 206%) and amygdala (WAY208466: sham-operated, NA -28%; lesioned, DA 302%; SB258585: sham-operated, NA 183%); however, 5-HT levels in these brain regions were not changed. These findings suggest DA depletion plays a key role in working and hippocampus-dependent memory impairments, and 5-HT6 receptors in the DH are involved in the regulation of the memories. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/27616337/Activation_and_blockade_of_serotonin6_receptors_in_the_dorsal_hippocampus_enhance_T_maze_and_hole_board_performance_in_a_unilateral_6_hydroxydopamine_rat_model_of_Parkinson's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(16)30617-5 DB - PRIME DP - Unbound Medicine ER -