title: Cocaine exposure alters dopaminergic modulation of prefronto-accumbens transmission.
abstract: In the nucleus accumbens (NAc), dopamine transmission modulates glutamatergic input from the prefrontal cortex (PFC). This neuromodulatory action of dopamine can be disrupted by repeated exposure to psychostimulants such as cocaine. However, it is unclear whether this modulation depends on the precise timing of transmission at the same medium spiny neurons (MSNs) and if so, then whether this timing related modulation is also influenced by cocaine experience. Here, combining cocaine self-administration and in vivo extracellular recordings in anesthetized rats, we show that dopamine efflux in the NAc evoked by electrically stimulating the ventral tegmental area (VTA) exerted timing-dependent regulation of the excitatory accumbens response to stimulation of the medial prefrontal cortex (mPFC), and also that this modulation was blunted following prolonged abstinence from cocaine self-administration. These data indicate that dopaminergic timing-dependent dysregulation of mPFC-NAc glutamatergic transmission is implicated in cocaine addiction and might contribute to vulnerability to drug relapse after prolonged abstinence.
authors.affiliation: Key Laboratory of Animal Resistance of Shandong Province, Department of Anatomy and Physiology, College of Life Science, Shandong Normal University, Jinan, China.
authors.forename: Xiusong
authors.initials: X
authors.lastname: Wang
authors.affiliation: The Second Hospital of Jilin University, Changchun, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Psychology, University of British Columbia, Vancouver, Canada.
authors.forename: Wendy
authors.initials: W
authors.lastname: Adams
authors.affiliation: Department of Psychology, Shandong Normal University, Jinan, China.
authors.forename: Shouxin
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Psychology, Shandong Normal University, Jinan, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: The Second Hospital of Jilin University, Changchun, China.
authors.forename: Bingjin
authors.initials: B
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Resistance of Shandong Province, Department of Anatomy and Physiology, College of Life Science, Shandong Normal University, Jinan, China. Electronic address: wangmin78@yahoo.com.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: The Second Hospital of Jilin University, Changchun, China. Electronic address: cuiranji@jlu.edu.cn.
authors.forename: Ranji
authors.initials: R
authors.lastname: Cui
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology*; D009714:Nucleus Accumbens / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration
chemical_list: D015259:Dopamine Agents; D018765:Dopamine Uptake Inhibitors; D003042:Cocaine; D004298:Dopamine
keywords: Cocaine self-administration; Dopamine; Nucleus accumbens; Prefrontal cortex; Ventral tegmental area