title: Pharmacological differences between rat frontal cortex and hippocampus in the nicotinic modulation of noradrenaline release implicate distinct receptor subtypes.
abstract: BACKGROUND
  Noradrenergic mechanisms in frontal cortex and hippocampus are relevant to attentional and stress-related aspects of addiction, respectively. Nicotinic receptors (nAChRs) modulate the release of noradrenaline (NA) in these tissues. This study determined if similar subtypes of nAChR regulate NA release in rat frontal cortex and hippocampus.
  
  
  METHODS
  The release of [(3)H]-NA from rat tissue prisms was characterized in a 96-well plate assay. In vivo microdialysis was used to monitor NA overflow from rat frontal cortex and hippocampus in conscious freely moving rats.
  
  
  RESULTS
  [(3)H]-NA release from frontal cortex prisms was more sensitive to nicotinic agonists than release from hippocampal prisms. The β2-selective agonist 5-iodo-A-85380 was 1000-fold more potent in frontal cortex compared with hippocampus. Agonist-evoked [(3)H]-NA release was inhibited by the β2-selective antagonist dihydro-beta-erythroidine (DHβE) in frontal cortex, whereas in hippocampal tissue, DHβE had no effect. In vivo, 5-iodo-A-85380 (1, 100 μM) applied locally via the dialysis probe, significantly increased NA overflow, compared with basal release, in frontal cortex but not in hippocampus.
  
  
  CONCLUSIONS
  These data support the modulation of NA release by different nAChR subtypes in frontal cortex and hippocampus. The pharmacological profile for rat hippocampus is consistent with previous studies, implicating α3β4* nAChRs in the modulation of NA release in this tissue. nAChRs having this function in frontal cortex are pharmacologically distinct and correspond to β2-containing nAChRs.
authors.affiliation: Department of Biology & Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, United Kingdom.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kennett
authors.forename: David J
authors.initials: DJ
authors.lastname: Heal
authors.forename: Susan
authors.initials: S
authors.lastname: Wonnacott
mesh_terms: D000818:Animals; D001384:Azetidines / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D017551:Microdialysis; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*
chemical_list: C426745:5-iodo-3-(2-azetidinylmethoxy)pyridine; D001384:Azetidines; D018765:Dopamine Uptake Inhibitors; D018722:Nicotinic Agonists; D010879:Piperazines; D011725:Pyridines; D011978:Receptors, Nicotinic; D009538:Nicotine; C043425:vanoxerine; D009638:Norepinephrine