Quantification and pharmacological characterization of dialysate levels of noradrenaline in the striatum of freely-moving rats: release from adrenergic terminals and modulation by α2-autoreceptors
2004
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 α 2 -adrenoceptor (AR) antagonist, atipamezole. The actions of atipamezole were mimicked by the preferential α 2A -AR antagonist, BRL44408, while JO-1 and prazosin, preferential antagonists at α 2C -ARs, caused less marked elevations in NA levels. In contrast to antagonists, the α 2 -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 D 3 /D 2 receptor agonist, quinelorane, decreased levels of DA without modifying those of NA. However, the D 3 /D 2 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 α 2 - and α 1 -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 α 2 -ARs, possibly involving both α 2A - and α 2C -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 D 3 /D 2 receptor antagonists.
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