title: Nicotinic acetylcholine receptors control acetylcholine and noradrenaline release in the rodent habenulo-interpeduncular complex.
abstract: OBJECTIVE
  Nicotinic acetylcholine receptors (nACh receptors) play a central role in the habenulo-interpeduncular system. We studied nicotine-induced release of NA and ACh in the habenula and interpeduncular nucleus (IPN).
  
  
  METHODS
  The habenula and IPN were loaded with [(3) H]-choline or [(3) H]-NA and placed in superfusion chambers. [(3) H]-ACh release was also stimulated using nicotinic agonists, electrical pulses and elevated [KCl]o in hippocampal and cortical slices from rats, wild-type mice and mice lacking α5, α7, β2, or β4 nACh receptor subunits. Finally, we analysed nACh receptor subtypes in the IPN using immunoprecipitation.
  
  
  RESULTS
  Nicotine induced release of [(3) H]-ACh in the IPN of rats and mice. This release was calcium-dependent but not blocked by tetrodotoxin (TTX); moreover, [(3) H]-ACh release was abolished in β4-knockout mice but was unaffected in β2- and α5-knockout mice. In contrast, nicotine-induced release of [(3) H]-NA in the IPN and habenula was blocked by TTX and reduced in both β2-knockout and β4-knockout mice, and dose-response curves were right-shifted in α5-knockout mice. Although electrical stimuli triggered the release of both transmitters, [(3) H]-ACh release required more pulses delivered at a higher frequency.
  
  
  CONCLUSIONS
  Our results confirm previous findings that β4-containing nACh receptors are critical for [(3) H]-ACh release in the mouse IPN. Experiments using α5-knockout mice also revealed that unlike in the hippocampus, nicotine-induced [(3) H]-NA release in the habenulo-interpeduncular system is altered in this knockout model. As α5-containing nACh receptors play a key role in nicotine intake, our results add NA to the list of transmitters involved in this mechanism.
authors.affiliation: Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, Vienna, Austria.
authors.forename: F
authors.initials: F
authors.lastname: Beiranvand
authors.forename: C
authors.initials: C
authors.lastname: Zlabinger
authors.forename: A
authors.initials: A
authors.lastname: Orr-Urtreger
authors.forename: R
authors.initials: R
authors.lastname: Ristl
authors.forename: S
authors.initials: S
authors.lastname: Huck
authors.forename: P
authors.initials: P
authors.lastname: Scholze
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D005260:Female; D019262:Habenula / Q000378:metabolism*; D066268:Interpeduncular Nucleus / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009638:Norepinephrine / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*
chemical_list: D021122:Protein Subunits; D011978:Receptors, Nicotinic; D000109:Acetylcholine; D009638:Norepinephrine