The role of CA3‐LS‐VTA loop in the formation of conditioned place preference induced by context‐associated reward memory for morphine

• DOI: 10.1111/adb.12468
• Publication Date: 2016-11-15T17:56:26Z
• Authors: Jin‐Xiang Jiang; Huan Liu; Zhen‐Zhen Huang; Yue Cui; Xue‐Qin Zhang; Xiao‐Long Zhang; Yu Cui; Wen‐Jun Xin
• Keywords: Male; Neurons; 0303 health sciences; Morphine; Glutamate Decarboxylase; Dopaminergic Neurons; Ventral Tegmental Area; Neural Inhibition; CA3 Region, Hippocampal; Rats; Analgesics, Opioid; Rats, Sprague-Dawley; 03 medical and health sciences; Reward; Memory; Conditioning, Psychological; Neural Pathways; Animals; Septal Nuclei; GABAergic Neurons

AbstractAddiction‐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.