Marked dissociation between high noradrenaline versus low noradrenaline transporter levels in human nucleus accumbens.
We recently identified a noradrenaline-rich caudomedial subdivision of the human nucleus accumbens (NACS), implying a special function for noradrenaline in this basal forebrain area involved in motivation and reward. To establish whether the NACS, as would be expected, contains similarly high levels of other noradrenergic markers, we measured dopamine-beta-hydroxylase (DBH) and noradrenaline transporter in the accumbens and, for comparison, in 23 other brain regions in autopsied human brains by immunoblotting. Although the caudomedial NACS had high DBH levels similar to those in other noradrenaline-rich areas, the noradrenaline transporter concentration was low (only 11% of that in hypothalamus). Within the accumbens, transporter concentration in the caudal portion was only slightly (by 30%) higher than that in the rostral subdivisions despite sharply increasing rostrocaudal gradients of noradrenaline (15-fold) and DBH. In contrast, the rostrocaudal gradient in the accumbens for the serotonin transporter and serotonin were similar (2-fold increase). The caudomedial NACS thus appears to represent the only instance in human brain having a striking mismatch in high levels of a monoamine neurotransmitter versus low levels of its uptake transporter. This suggests that noradrenaline signalling is much less spatially and temporally restricted in the caudomedial accumbens than in other noradrenaline-rich brain areas.
Tong
Junchao
J
Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, CanadaCenter for Brain Research, Medical University of Vienna, Spitalgasse, Vienna, AustriaMovement Disorders Research Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Hornykiewicz
Oleh
O
Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, CanadaCenter for Brain Research, Medical University of Vienna, Spitalgasse, Vienna, AustriaMovement Disorders Research Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Furukawa
Yoshiaki
Y
Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, CanadaCenter for Brain Research, Medical University of Vienna, Spitalgasse, Vienna, AustriaMovement Disorders Research Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Kish
Stephen J
SJ
Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, CanadaCenter for Brain Research, Medical University of Vienna, Spitalgasse, Vienna, AustriaMovement Disorders Research Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
D000328:Adult; D004298:Dopamine / Q000378:metabolism; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000378:metabolism*; D011180:Postmortem Changes; D012701:Serotonin / Q000378:metabolism; D013223:Statistics as Topic; D014018:Tissue Distribution
D050484:Norepinephrine Plasma Membrane Transport Proteins; D012701:Serotonin; D004299:Dopamine beta-Hydroxylase; D004298:Dopamine; D009638:Norepinephrine