title: Cocaine cues drive opposing context-dependent shifts in reward processing and emotional state.
abstract: BACKGROUND
  Prominent neurobiological theories of addiction posit a central role for aberrant mesolimbic dopamine release but disagree as to whether repeated drug experience blunts or enhances this system. Although drug withdrawal diminishes dopamine release, drug sensitization augments mesolimbic function, and both processes have been linked to drug seeking. One possibility is that the dopamine system can rapidly switch from dampened to enhanced release depending on the specific drug-predictive environment. To test this, we examined dopamine release when cues signaled delayed cocaine delivery versus imminent cocaine self-administration.
  
  
  METHODS
  Fast-scan cyclic voltammetry was used to examine real-time dopamine release while simultaneously monitoring behavioral indexes of aversion as rats experienced a sweet taste cue that predicted delayed cocaine availability and during self-administration. Furthermore, the impact of cues signaling delayed drug availability on intracranial self-stimulation, a broad measure of reward function, was assessed.
  
  
  RESULTS
  We observed decreased mesolimbic dopamine concentrations, decreased reward sensitivity, and negative affect in response to the cocaine-predictive taste cue that signaled delayed cocaine availability. Importantly, dopamine concentration rapidly switched to elevated levels to cues signaling imminent cocaine delivery in the subsequent self-administration session.
  
  
  CONCLUSIONS
  These findings show rapid, bivalent contextual control over brain reward processing, affect, and motivated behavior and have implications for mechanisms mediating substance abuse.
authors.affiliation: Department of Psychology, University of North Carolina, Chapel Hill, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wheeler
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Aragona
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Fuhrmann
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Jones
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Day
authors.forename: Fabio
authors.initials: F
authors.lastname: Cacciapaglia
authors.forename: R Mark
authors.initials: RM
authors.lastname: Wightman
authors.forename: Regina M
authors.initials: RM
authors.lastname: Carelli
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003042:Cocaine / Q000008:administration & dosage*; D003463:Cues; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004328:Drive; D004563:Electrochemistry; D004644:Emotions / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D012646:Self Administration
chemical_list: D018765:Dopamine Uptake Inhibitors; D003042:Cocaine; D004298:Dopamine