In vivo dynamics of norepinephrine release-reuptake in multiple terminal field regions of rat brain.
Electrical stimulation of the ascending dorsal tegmental bundle of the locus ceruleus was used to elicit controlled release of norepinephrine. Real-time in vivo monitoring in the brains of urethane-anesthetized rats was observed with high speed chronocoulometry at rapidly responding carbon fiber electrodes. Using modeling similar to that developed for dopamine release, the electrochemical signals were characterized as the balance between norepinephrine release per electrical stimulation pulse and apparent Michaelis-Menten reuptake parameters. Stimulation produced simultaneous overflow release at all terminal fields examined. The release and reuptake characteristics varied considerably in different regions. If the parameters are normalized to endogenous concentration in the terminal fields, release but not reuptake correlates with innervation density in several regions. Stimulated release results in norepinephrine overflow and transport in most brain regions with half-lives of 1-3 s and overflow distances of 25-50 microns at most. A surprising exception occurs in the upper layers of cortex (cingulate and sensory) where half-lives may be in the 10s of seconds and spatial reach may be up to 100 microns. The uptake in the outer cortical layers appears to be minimal and comparable with only nonspecific reuptake.
Mitchell
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Department of Chemistry, University of Kansas, Lawrence 66045.
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Adams
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D000818:Animals; D001921:Brain / Q000502:physiology*; D004558:Electric Stimulation; D004563:Electrochemistry; D007700:Kinetics; D008125:Locus Coeruleus / Q000502:physiology; D008954:Models, Biological; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats
D009638:Norepinephrine