title: Nicotinic acetylcholine receptors in the ventral tegmental area mediate the dopamine activating and reinforcing properties of ethanol cues.
abstract: BACKGROUND
  Cues associated with alcohol can elicit craving, support drug-seeking and precipitate relapse.
  
  
  OBJECTIVE
  We investigated the possible involvement of nicotinic acetylcholine receptors (nAChRs) in the ventral tegmental area (VTA) in the conditioned reinforcing properties of ethanol-associated stimuli in the rat.
  
  
  METHODS
  First, using in vivo microdialysis, we analyzed the effect of VTA perfusion of the nonselective nAChR antagonist mecamylamine (MEC) or the selective alpha4beta2* nAChR antagonist dihydro-beta-erythroidine (DHbetaE) on the nucleus accumbens (nAc) dopaminergic response to the presentation of an ethanol-associated conditioned stimulus (CS). Second, rats were trained to associate a tone+light CS with the presentation of 10% ethanol and were subsequently tested on the acquisition of a new instrumental response with conditioned reinforcement (CR) after local VTA infusion of MEC, DHbetaE, or alpha-Conotoxin MII (alpha-CtxMII, a selective alpha3beta2* and alpha6* nAChR antagonist).
  
  
  RESULTS
  The ethanol-associated CS elevated nAc dopamine, an effect that was blocked by VTA perfusion of MEC but not DHbetaE. Systemic administration of MEC or local VTA infusion of MEC or alpha-CtxMII selectively blocked ethanol-associated CR, whereas systemic DHbetaE had no effect.
  
  
  CONCLUSIONS
  We hypothesize a novel mechanism by which alcohol-associated cues promote drug-seeking behavior via activation of dopamine-stimulating alpha-CtxMII-sensitive nAChRs in the VTA. Pharmacological manipulations of selective nAChRs may thus be possible treatment strategies to prevent cue-induced relapse.
authors: Inst. Neuroscience and Physiology, Sect. Psychiatry and Neurochemistry, Sahlgrenska Academy, Göteborg University and Beroendekliniken, Sahlgrenska University Hospital, Gothenburg, Sweden. elin.lof@neuro.gu.se
authors: Elin
authors: E
authors: Löf
authors: Peter
authors: P
authors: Olausson
authors: Andrea
authors: A
authors: deBejczy
authors: Rosita
authors: R
authors: Stomberg
authors: J Michael
authors: JM
authors: McIntosh
authors: Jane R
authors: JR
authors: Taylor
authors: Bo
authors: B
authors: Söderpalm
mesh_terms: D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D020916:Conotoxins / Q000494:pharmacology; D003463:Cues; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D017551:Microdialysis; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000502:physiology*; D012054:Reinforcement, Psychology; D012646:Self Administration; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism
chemical_list: D020916:Conotoxins; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; C098872:alpha-conotoxin MII; D004079:Dihydro-beta-Erythroidine; D000431:Ethanol; D008464:Mecamylamine; D004298:Dopamine
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