title: The role of CA3-LS-VTA loop in the formation of conditioned place preference induced by context-associated reward memory for morphine.
abstract: Addiction-related behaviors, such as conditioned place preference (CPP), require animals to remember an association between environmental cue and drug treatment, and exposure to environmental cue is one of the key contributing factors to relapse. However, how central neural circuit participates in the formation of CPP induced by stimulus of morphine-paired environment remains unknown. In the present study, we found that reexposure to morphine-paired environment significantly increased the activity of hippocampal CA3 neurons, increased the excitability of GABAergic neurons and expression of glutamic acid decarboxylase 65/67 in the caudal lateral septum (LSc) and decreased the activity of GABAergic neurons and GAD65/67 expression in ventral tegmental area (VTA), leading to activation (disinhibition) of dopaminergic neurons. Inactivation of CA3 neurons attenuated GABAergic neurons activity and decreased the upregulation of GAD65/67 in LSc, prevented the dopaminergic neurons activation,and GAD65/67 downregulation in VTA and ameliorated the CPP behavior following exposure to morphine-paired context. Blockade of NMDA receptor in LSc also prevented the upregulation of GAD65/67 in LSc and formation of CPP induced by stimulus of morphine-paired environment. Suppression of GAD activity in LSc also remarkably attenuated the dopaminergic neurons activation and the GAD65/67 downregulation in VTA and prevented the formation of CPP induced by reexposure to morphine-associated context. Collectively, these results, for the first time, illustrated the involvement of neural circuitry of CA3-LSc-VTA, through integration of the contexts and reward information, participated in the reinstatement of CPP induced by exposure to morphine-associated context, which advanced our understanding on neurobiological basis for the context-associated memory and rewarding behavior.
authors.affiliation: Department of Psychology, Guangzhou Medical University, China.
authors.forename: Jin-Xiang
authors.initials: JX
authors.lastname: Jiang
authors.affiliation: Guangdong Province Key Laboratory of Brain Function and Disease, Department of Forensic Medicine, Zhongshan Medical School, Sun Yat-Sen University, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Guangdong Province Key Laboratory of Brain Function and Disease, Department of Forensic Medicine, Zhongshan Medical School, Sun Yat-Sen University, China.
authors.forename: Zhen-Zhen
authors.initials: ZZ
authors.lastname: Huang
authors.affiliation: Department of Physiology, Shenyang Medical College, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Psychology, Guangzhou Medical University, China.|Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, China.
authors.forename: Xue-Qin
authors.initials: XQ
authors.lastname: Zhang
authors.affiliation: Guangdong Province Key Laboratory of Brain Function and Disease, Department of Forensic Medicine, Zhongshan Medical School, Sun Yat-Sen University, China.
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Zhang
authors.affiliation: Guangdong Province Key Laboratory of Brain Function and Disease, Department of Forensic Medicine, Zhongshan Medical School, Sun Yat-Sen University, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Guangdong Province Key Laboratory of Brain Function and Disease, Department of Forensic Medicine, Zhongshan Medical School, Sun Yat-Sen University, China.
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Xin
mesh_terms: D000701:Analgesics, Opioid; D000818:Animals; D056654:CA3 Region, Hippocampal / Q000166:cytology / Q000378:metabolism*; D003213:Conditioning, Psychological / Q000502:physiology*; D059290:Dopaminergic Neurons / Q000166:cytology / Q000378:metabolism*; D059330:GABAergic Neurons / Q000166:cytology / Q000378:metabolism*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008297:Male; D008568:Memory; D009020:Morphine; D009433:Neural Inhibition; D009434:Neural Pathways; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D012686:Septal Nuclei / Q000166:cytology / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000166:cytology / Q000378:metabolism*
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2
keywords: conditioned place preference; lateral septum; morphine