Quantification and pharmacological characterization of dialysate levels of noradrenaline in the striatum of freely-moving rats: release from adrenergic terminals and modulation by alpha2-autoreceptors

J Neurosci Methods. 2004 Dec 30;140(1-2):141-52. doi: 10.1016/j.jneumeth.2004.04.040.

Abstract

Information concerning striatal levels of noradrenaline (NA) remains inconsistent. Here we have addressed this issue using a sensitive method of HPLC coupled to amperometric detection. The NA reuptake-inhibitor, reboxetine, selectively elevated levels of NA versus dopamine (DA), and NA levels were also selectively elevated by the alpha2-adrenoceptor (AR) antagonist, atipamezole. The actions of atipamezole were mimicked by the preferential alpha2A-AR antagonist, BRL44408, while JO-1 and prazosin, preferential antagonists at alpha2C-ARs, caused less marked elevations in NA levels. In contrast to antagonists, the alpha2-AR agonist, S18616, decreased NA levels and likewise suppressed those of DA. Unilateral lesions of the substantia nigra with 6-hydroxydopamine depleted DA levels without affecting those of NA. Further, the D3/D2 receptor agonist, quinelorane, decreased levels of DA without modifying those of NA. However, the D3/D2 receptor antagonists, haloperidol and raclopride, and the DA reuptake-inhibitor, GBR12935, elevated levels of both DA and NA. Levels of 5-HT (but not of NA or DA) were increased only by the 5-HT reuptake-inhibitor, citalopram. They were decreased by S18616 and prazosin, reflecting the inhibitory and excitatory influence of alpha2- and alpha1-ARs, respectively, upon serotonergic pathways. In conclusion, NA in the striatum is derived from adrenergic terminals. Its release is subject to tonic, inhibitory control by alpha2-ARs, possibly involving both alpha2A- and alpha2C-AR subtypes, though their respective contribution requires clarification. A role of dopaminergic terminals in the reuptake of NA likely explains the elevation in its levels elicited by DA reuptake-inhibitors and D3/D2 receptor antagonists.

MeSH terms

  • Adrenergic Uptake Inhibitors / pharmacology
  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Autoreceptors / drug effects
  • Autoreceptors / metabolism*
  • Chromatography, High Pressure Liquid
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Dopamine / metabolism
  • Extracellular Fluid / drug effects
  • Extracellular Fluid / metabolism
  • Male
  • Microdialysis
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Neural Pathways / drug effects
  • Neural Pathways / metabolism*
  • Norepinephrine / analysis
  • Norepinephrine / metabolism*
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism*
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, alpha-2 / drug effects
  • Receptors, Adrenergic, alpha-2 / metabolism*
  • Receptors, Dopamine / drug effects
  • Receptors, Dopamine / metabolism
  • Serotonin / metabolism
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism
  • Substantia Nigra / physiopathology

Substances

  • Adrenergic Uptake Inhibitors
  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Autoreceptors
  • Receptors, Adrenergic, alpha-2
  • Receptors, Dopamine
  • Serotonin
  • Dopamine
  • Norepinephrine