title: Prefrontal cortex gates acute morphine action on dopamine neurons in the ventral tegmental area.
abstract: Morphine excites dopamine (DA) neurons in the ventral tegmental area (VTA), an effect mediated by both local and systemic mechanisms. While the importance of the prefrontal cortex (PFC) - VTA circuit in opiate addiction is well established, little is known about how the PFC regulates the activity of VTA DA neurons upon morphine stimulation. One major challenge is that VTA DA neurons are highly heterogeneous in terms of projection and regulation, making their responses to PFC manipulations variable. Our previous work has identified a subgroup of VTA DA neurons exhibiting significant slow oscillation in their firing sequence, and demonstrated that most of these neurons are functionally connected with the PFC. In the present study, we focus our efforts only on VTA DA neurons expressing strong slow oscillation, and report that blocking the neuronal activity in the PFC remarkably attenuates the morphine-induced excitation of these neurons. Using in vivo microdialysis, we find that inactivation of the PFC also reduces the morphine-induced elevation of DA levels in the nucleus accumbens (NAc). Furthermore, 24 h after only single morphine exposure, PFC-inactivation failed to prevent subsequent morphine challenge from exciting VTA DA neurons, which is paralleled by altered response of PFC pyramidal neurons to morphine stimulation. Our results indicate that the PFC gates acute morphine action on a subset of VTA DA neurons, which is highly plastic and can be functionally remodeled by morphine exposure.
authors.affiliation: Department of Pharmacology, State Key Laboratory of Drug Research, Institute of Materia Medica, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China; Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Department of Pharmacology, Soochow University, College of Pharmaceutical Sciences, Suzhou 215006, China.
authors.forename: Changliang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Department of Pharmacology, Soochow University, College of Pharmaceutical Sciences, Suzhou 215006, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Fang
authors.affiliation: Department of Pharmacology, State Key Laboratory of Drug Research, Institute of Materia Medica, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, State Key Laboratory of Drug Research, Institute of Materia Medica, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Guozhang
authors.initials: G
authors.lastname: Jin
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Department of Pharmacology, Soochow University, College of Pharmaceutical Sciences, Suzhou 215006, China. Electronic address: zhenxuechu@suda.edu.cn.
authors.forename: Xuechu
authors.initials: X
authors.lastname: Zhen
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000502:physiology; D008297:Male; D017551:Microdialysis; D008839:Microelectrodes; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D010507:Periodicity; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D017207:Rats, Sprague-Dawley; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000502:physiology
chemical_list: D009294:Narcotics; D009020:Morphine; D004298:Dopamine
keywords: Dopamine; Morphine; Prefrontal cortex; Single-unit recording; Ventral tegmental area