title: Dopamine D1 receptor blockade impairs alcohol seeking without reducing dorsal striatal activation to cues of alcohol availability.
abstract: BACKGROUND
  Alcohol-associated cues activate both ventral and dorsal striatum in functional brain imaging studies of heavy drinkers. In rodents, alcohol-associated cues induce changes in neuronal firing frequencies and increase dopamine release in ventral striatum, but the impact of alcohol-associated cues on neuronal activity in dorsal striatum is unclear. We previously reported phasic changes in action potential frequency in the dorsomedial and dorsolateral striatum after cues that signaled alcohol availability, prompting approach behavior.
  
  
  METHODS
  We investigated the hypothesis that dopamine transmission modulates these phasic firing changes. Rats were trained to self-administer alcohol, and neuronal activity was monitored with extracellular electrophysiology during "anticipatory" cues that signaled the start of the operant session. Sessions were preceded by systemic administration of the D1-type dopamine receptor antagonist SCH23390 (0, 10, and 20 μg/kg).
  
  
  RESULTS
  SCH23390 significantly decreased firing rates during the 60 s prior to cue onset without reducing phasic excitations immediately following the cues. While neuronal activation to cues might be expected to initiate behavioral responses, in this study alcohol seeking was reduced despite the presence of dorsal striatal excitations to alcohol cues.
  
  
  CONCLUSIONS
  These data suggest that D1 receptor antagonism reduces basal firing rates in the dorsal striatum and modulates the ability of neuronal activation to "anticipatory" cues to initiate alcohol seeking in rats with an extensive history of alcohol self-administration.
authors: Neurobiology Curriculum, University of North Carolina Chapel Hill, North Carolina ; Bowles Center for Alcohol Studies, University of North Carolina Chapel Hill, North Carolina.
authors: Rebecca R
authors: RR
authors: Fanelli
authors: Neurobiology Curriculum, University of North Carolina Chapel Hill, North Carolina ; Bowles Center for Alcohol Studies, University of North Carolina Chapel Hill, North Carolina ; Department of Psychiatry, University of North Carolina Chapel Hill, North Carolina.
authors: Donita L
authors: DL
authors: Robinson
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003463:Cues; D004298:Dopamine / Q000378:metabolism; D008297:Male; D011897:Random Allocation; D051381:Rats; D020318:Rats, Long-Evans; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D012646:Self Administration; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D001552:Benzazepines; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D004298:Dopamine
keywords: RRID:nif-0000-31484; RRID:nlx_153890; RRID:nlx_157643; RRID:nlx_158483; RRID:nlx_158484; RRID:nlx_158504; dopamine D1 receptor antagonist SCH23390; dorsolateral striatum; dorsomedial striatum; extracellular electrophysiology
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