title: Catecholamine outflow from mouse and rat brain slice preparations evoked by nicotinic acetylcholine receptor activation and electrical field stimulation.
abstract: OBJECTIVE
  Mice with targeted deletions of neuronal nicotinic acetylcholine receptor (nAChR) subunit genes are valuable models to study nAChR function such as catecholamine outflow by presynaptic receptor activation. Contrary to the rat, our present knowledge on presynaptic nAChRs in mice primarily relies on observations made with synaptosomes. We have now used brain slices to investigate nicotine-induced catecholamine outflow in wild type (WT) and nAChR (beta2 and alpha5) knockout mice for a comparison with rat brain slice preparations.
  
  
  METHODS
  Brain slices from rat and mouse hippocampus, parieto-occipital neocortex, and corpus striatum were loaded with either [3H]-noradrenaline or [3H]-dopamine. We provoked catecholamine outflow by electrical field stimulation and nicotinic agonists.
  
  
  RESULTS
  When set in relation to electrical field stimulation, nicotine-evoked catecholamine release was sizeable in the striatum but low in the neocortex of both rats and mice. [3H]-noradrenaline outflow was, on the other hand, substantial in the rat but low in the mouse hippocampus. About 10% (or less) of nicotine-induced catecholamine release persisted in the presence of tetrodotoxin in all our preparations.
  
  
  CONCLUSIONS
  Targeted deletion of the beta2 subunit gene essentially abolished the effect of nicotine, indicating that this subunit is an essential constituent of nAChRs that indirectly (via action potentials) induce catecholamine release from hippocampal and striatal slices in mice. The impact of nAChRs in catecholaminergic projection areas differs between species and has thus to be considered when extrapolating results from animal models to human conditions.
authors.affiliation: Center for Brain Research, Medical University of Vienna, Vienna, Austria.
authors.forename: P
authors.initials: P
authors.lastname: Scholze
authors.forename: A
authors.initials: A
authors.lastname: Orr-Urtreger
authors.forename: J-P
authors.initials: JP
authors.lastname: Changeux
authors.forename: J M
authors.initials: JM
authors.lastname: McIntosh
authors.forename: S
authors.initials: S
authors.lastname: Huck
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001392:Azocines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019579:Neocortex / Q000187:drug effects / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D021122:Protein Subunits / Q000819:agonists / Q000235:genetics / Q000502:physiology; D011807:Quinolizines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000235:genetics / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D000093843:Quinolizidine Alkaloids
chemical_list: D000470:Alkaloids; D001392:Azocines; D002395:Catecholamines; D004246:Dimethylphenylpiperazinium Iodide; D004298:Dopamine; D009538:Nicotine; D018722:Nicotinic Agonists; D009638:Norepinephrine; D021122:Protein Subunits; D011807:Quinolizines; D011978:Receptors, Nicotinic; D013779:Tetrodotoxin; C004712:cytisine; D000093843:Quinolizidine Alkaloids