Simultaneous measurement of plasma and brain extracellular fluid concentrations of catechols after yohimbine administration in rats.
The present study examined whether systemic injection of the alpha 2 adrenoceptor blocker, yohimbine, affects concentrations of norepinephrine (NE) and its metabolites in extracellular fluid in the brain and in blood. Microdialysis probes were inserted into the posterior hypothalamus, medulla, and caudate/putamen in rats. Microdialysate and arterial blood were sampled after intravenous administration of yohimbine. In the hypothalamus yohimbine produced significant increases in extracellular fluid concentrations of NE, its intraneuronal metabolite, dihydroxyphenylglycol (DHPG), and methoxyhydroxyphenylglycol (MHPG), a major neuronal and extraneuronal metabolite of NE. The increases in these levels were small or absent in the caudate/putamen, where dopamine is the primary catecholamine transmitter. During systemic infusion of tracer amounts of [3H]NE, little if any radioactive NE or DHPG appeared in the microdialysate, whereas substantial levels of [3H]MHPG were present and increased as plasma [3H]MHPG levels rose. The results support the view that alpha 2 adrenoceptor blockade in the brain increases hypothalamic and medullary release, reuptake, and metabolism of NE. The findings cannot be explained by disruption of the blood-brain barrier for catecholamines by insertion of the microdialysis probes. Enhanced sympathetic outflow and peripheral release of NE when alpha 2 adrenoceptors are blocked appears to be attended by enhanced central NE release, presumably as a result of presynaptic alpha 2 adrenoceptor blockade at noradrenergic terminals in the brain. This is consistent with the hypothesis that central noradrenergic NE release is regulated by presynaptic alpha 2 adrenoceptors.
Szemeredi
K
K
Hypertensive-Endocrine Branch, National Heart, Lung, and Blood Institute, Bethesda, MD 20892.
Komoly
S
S
Kopin
I J
IJ
Bagdy
G
G
Keiser
H R
HR
Goldstein
D S
DS
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002396:Catechols / Q000097:blood* / Q000378:metabolism; D003956:Dialysis / Q000379:methods; D005110:Extracellular Space / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism; D009994:Osmolar Concentration; D051381:Rats; D011921:Rats, Inbred WKY; D015016:Yohimbine / Q000494:pharmacology*
D002396:Catechols; D015016:Yohimbine; D009638:Norepinephrine