title: Dysregulation of dopamine and glutamate release in the prefrontal cortex and nucleus accumbens following methamphetamine self-administration and during reinstatement in rats.
abstract: Methamphetamine (meth) addicts often exhibit enduring cognitive and neural deficits that likely contribute to persistent drug seeking and the high rates of relapse. These deficits may be related to changes in the prefrontal cortex (PFC) and its glutamatergic projections to the nucleus accumbens (NAc). Here, we performed in vivo microdialysis in the PFC and NAc in rats following either meth self-administration or yoked-saline control histories to assess baseline glutamate (GLU) levels, or reinstatement-evoked GLU and dopamine (DA) efflux in both regions simultaneously under cue-induced, meth-primed, or combined cues+meth reinstatement conditions. Our results show that meth self-administration (1) reduced basal GLU levels in both the dmPFC and NAc, (2) concurrently increased dmPFC and NAc GLU efflux during reinstatement, and (3) increased DA efflux in the dmPFC, but not in the NAc, under all reinstatement conditions when compared with yoked-saline controls. These data demonstrate for the first time that a history of psychostimulant self-administration alters GLU homeostasis not only in the NAc, but also in the dmPFC, its primary GLU projection source. Furthermore, combined cues+meth-primed reinstatement conditions produced the most pronounced increases in mPFC and NAc extracellular GLU, suggesting that the cue and meth prime conditions are additive in promoting reinstatement. Finally, increased efflux of DA in the dmPFC, but not in the NAc, across reinstatement conditions suggests that DA release in the dmPFC may be an important mediator of drug seeking initiated by multiple relapse triggers.
authors.affiliation: Department of Neurosciences, Medical University of South Carolina Charleston, Charleston, SC, USA.
authors.forename: Aram
authors.initials: A
authors.lastname: Parsegian
authors.affiliation: 1] Department of Neurosciences, Medical University of South Carolina Charleston, Charleston, SC, USA [2] Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: See
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D002851:Chromatography, High Pressure Liquid; D003216:Conditioning, Operant / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D058999:Drug-Seeking Behavior / Q000187:drug effects; D005108:Extinction, Psychological / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000187:drug effects*; D051381:Rats; D020318:Rats, Long-Evans; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration
chemical_list: D000697:Central Nervous System Stimulants; D018698:Glutamic Acid; D008694:Methamphetamine; D004298:Dopamine