title: Regional influence of cocaine on evoked dopamine release in the nucleus accumbens core: A role for the caudal brainstem.
abstract: Cocaine increases dopamine concentration in the nucleus accumbens through competitive binding to the dopamine transporter (DAT). However, it also increases the frequency of dopamine release events, a finding that cannot be explained by action at the DAT alone. Rather, this effect may be mediated by cocaine-induced modulation of brain regions that project to dopamine neurons. To explore regional contributions of cocaine to dopamine signaling, we administered cocaine to the lateral or fourth ventricles and compared the effects on dopamine release in the nucleus accumbens evoked by electrical stimulation of the ventral tegmental area to that of systemically-delivered cocaine. Stimulation trains caused a sharp rise in dopamine followed by a slower return to baseline. The magnitude of dopamine release ([DA]max) as well as the latency to decay to fifty percent of the maximum (t(1/2); index of DAT activity) by each stimulation train were recorded. All routes of cocaine delivery caused an increase in [DA]max; only systemic cocaine caused an increase in t(1/2). Importantly, these data are the first to show that hindbrain (fourth ventricle)-delivered cocaine modulates phasic dopamine signaling. Fourth ventricular cocaine robustly increased cFos immunoreactivity in the nucleus of the solitary tract (NTS), suggesting a neural substrate for hindbrain cocaine-mediated effects on [DA]max. Together, the data demonstrate that cocaine-induced effects on phasic dopamine signaling are mediated via actions throughout the brain including the hindbrain.
authors: Department of Psychology, University of Illinois at Chicago, 1007 W Harrison St, Chicago, IL 60607, USA.
authors: Ashlynn I
authors: AI
authors: Gerth
authors: Department of Psychology, University of Pennsylvania, 3720 Walnut St, Philadelphia, PA 19104, USA.
authors: Amber L
authors: AL
authors: Alhadeff
authors: Department of Psychology, University of Pennsylvania, 3720 Walnut St, Philadelphia, PA 19104, USA.
authors: Harvey J
authors: HJ
authors: Grill
authors: Department of Psychology, University of Illinois at Chicago, 1007 W Harrison St, Chicago, IL 60607, USA. Electronic address: mroitman@uic.edu.
authors: Mitchell F
authors: MF
authors: Roitman
mesh_terms: D000818:Animals; D002452:Cell Count; D003042:Cocaine / Q000008:administration & dosage*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004558:Electric Stimulation; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012249:Rhombencephalon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
chemical_list: D018765:Dopamine Uptake Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D003042:Cocaine; D004298:Dopamine
keywords: Cocaine; Dopamine; Drug addiction; Nucleus accumbens; Reward; Voltammetry