Regional differences in the in vivo regulation of the extracellular levels of noradrenaline and its metabolites in rat brain.
Microdialysis was used to determine extracellular levels of both noradrenaline and its metabolites in several brain regions of rats under basal conditions and in response to drugs selective for the alpha 2-adrenoceptor to study regional differences in the regulation of noradrenaline overflow. Basal overflow of noradrenaline was about 1.3 fmol/min in frontoparietal cortex, amygdala and hippocampus and in the medial prefrontal cortex 2.4 fmol/min was measured, whereas the overflow of the noradrenaline metabolites 3,4-dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol was 10-fold higher. After correction for recovery and membrane length no regional differences in the basal overflow of noradrenaline (NA) were found. There were, however, regional differences in the drug-induced effects: locally applied moxonidine decreased extracellular noradrenaline stronger in the frontoparietal cortex than in the medial prefrontal cortex. The increase in noradrenaline overflow caused by idazoxan (10(-4) M) was stronger in frontoparietal cortex than in amygdala and hippocampus. The metabolites were also generally decreased by moxonidine and increased by idazoxan, although less markedly. The present study shows that the regulation of noradrenaline overflow by the presynaptic alpha 2-autoreceptor was stronger in cortical regions than in amygdala and hippocampus. In those latter regions the uptake mechanism probably plays a relatively more important role in the regulation of noradrenaline overflow.
van Veldhuizen
M J
MJ
Graduate School Neurosciences Amsterdam, Netherlands Institute for Brain Research.
Feenstra
M G
MG
Boer
G J
GJ
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004146:Dioxanes / Q000494:pharmacology; D019329:Idazoxan; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000378:metabolism*; D017551:Microdialysis; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D007093:Imidazoles; D008734:Methoxyhydroxyphenylglycol; C043482:moxonidine; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine; D019329:Idazoxan