title: Ventral tegmental area α6β2 nicotinic acetylcholine receptors modulate phasic dopamine release in the nucleus accumbens core.
abstract: BACKGROUND
  Phasic dopamine (DA) signaling underlies reward learning. Cholinergic and glutamatergic inputs into the ventral tegmental area (VTA) are crucial for modulating burst firing activity and subsequent phasic DA release in the nucleus accumbens (NAc), but the specific VTA nicotinic receptor subtypes that regulate phasic DA release have not been identified.
  
  
  OBJECTIVE
  The goal was to determine the role of VTA N-methyl-D-aspartate receptors (NMDARs) and specific subtypes of nicotinic acetylcholine receptors (nAChRs) in regulating phasic DA release in the NAc core.
  
  
  METHODS
  Fast-scan cyclic voltammetry in anesthetized rats was combined with intra-VTA micro-infusion to evaluate the ability of glutamatergic and cholinergic drugs to modulate stimulated phasic DA release in the NAc core.
  
  
  RESULTS
  VTA NMDAR blockade with AP-5 decreased, while VTA NMDAR activation with NMDA increased NAc peak phasic DA release. Intra-VTA administration of the nonspecific nAChR antagonist mecamylamine produced a persistent decrease in phasic DA release. Infusion of the α6-selective antagonist α-conotoxin MII (α-ctx MII) produced a robust, but transient decrease in phasic DA, whereas infusion of selective doses of either the α4β2-selective antagonist, dihydro-beta-erythroidine, or the α7 antagonist, methyllycaconitine, had no effect. Co-infusion of AP-5 and α-ctx MII produced a similar phasic DA decrease as either drug alone, with no additive effect.
  
  
  CONCLUSIONS
  The results suggest that VTA α6β2 nAChRs, but not α4β2 or α7 nAChRs, regulate phasic DA release in the NAc core and that VTA α6β2 nAChRs and NMDA receptors act at a common site or target to regulate NAc phasic DA signaling.
authors.affiliation: Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT 06511, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Wickham
authors.forename: Wojciech
authors.initials: W
authors.lastname: Solecki
authors.forename: Liza
authors.initials: L
authors.lastname: Rathbun
authors.forename: J Michael
authors.initials: JM
authors.lastname: McIntosh
authors.forename: Nii A
authors.initials: NA
authors.lastname: Addy
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000502:physiology*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism*
chemical_list: D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; C559463:alpha6beta2 nicotinic acetylcholine receptor; D004298:Dopamine