title: Characterization of noradrenaline release in the locus coeruleus of freely moving awake rats by in vivo microdialysis.
abstract: BACKGROUND
  The origin and regulation of noradrenaline (NA) in the locus coeruleus (LC) is unknown.
  
  
  OBJECTIVE
  The neurochemical features of NA overflow (nerve impulse dependence, neurotransmitter synthesis, vesicle storage, reuptake, alpha2-adrenoceptor-mediated regulation) were characterized in the LC.
  
  
  METHODS
  Brain microdialysis was performed in awake rats. Dialysates were analyzed for NA.
  
  
  RESULTS
  NA in the LC decreased via local infusion of Ca2+-free medium (-42+/-5%) or the sodium channel blocker tetrodotoxine (TTX) (-47+/-8%) but increased (333+/-40%) via KCl-induced depolarization. The tyrosine hydroxylase (TH) inhibitor alpha-methyl-p-tyrosine (250 mg kg(-1), i.p.) and the vesicle depletory drug reserpine (5 mg kg(-1), i.p.) decreased NA. Therefore, extracellular NA in the LC satisfies the criteria for an impulse flow-dependent vesicular exocytosis of neuronal origin. Local perfusion of the alpha2-adrenoceptor agonist clonidine (0.1-100 microM) decreased NA (E(max)=-79+/-5%) in the LC, whereas the opposite effect (E(max)=268+/-53%) was observed with the alpha2A-adrenoceptor antagonist BRL44408 (0.1-100 microM). This suggests a tonic modulation of NA release through local alpha2A-adrenoceptors. The selective NA reuptake inhibitor desipramine (DMI) (0.1-100 microM) administered into the LC increased NA in the LC (E(max)=223+/-40%) and simultaneously decreased NA in the cingulate cortex, confirming the modulation exerted by NA in the LC on firing activity of noradrenergic cells and on the subsequent NA release in noradrenergic terminals.
  
  
  CONCLUSIONS
  Synaptic processes underlying NA release in the LC are similar to those in noradrenergic terminal areas. NA in the LC could represent local somatodendritic release, but also the presence of neurotransmitter release from collateral axon terminals.
authors.affiliation: Department of Pharmacology, University of Basque Country, 48940 Leioa, Bizkaia, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Fernández-Pastor
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Mateo
authors.forename: Sonia
authors.initials: S
authors.lastname: Gómez-Urquijo
authors.forename: J
authors.initials: J
authors.lastname: Javier Meana
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D002555:Cerebrospinal Fluid / Q000737:chemistry; D003000:Clonidine / Q000494:pharmacology; D015314:Dialysis Solutions / Q000008:administration & dosage / Q000737:chemistry; D045604:Extracellular Fluid / Q000737:chemistry / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D008125:Locus Coeruleus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism; D013779:Tetrodotoxin / Q000008:administration & dosage / Q000494:pharmacology; D014851:Wakefulness / Q000502:physiology; D019805:alpha-Methyltyrosine / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D014150:Antipsychotic Agents; D015314:Dialysis Solutions; D007093:Imidazoles; D007211:Indoles; D054833:Isoindoles; D013779:Tetrodotoxin; D019805:alpha-Methyltyrosine; D011189:Potassium Chloride; D012110:Reserpine; D003000:Clonidine; D009638:Norepinephrine; C072125:BRL 44408
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