Correlation between the inhibitory effect on catecholaminergic ventrolateral medullary neurons and the hypotension evoked by clonidine: a voltammetric approach.
Neuronal activity was monitored in vivo by differential voltammetry, an electrochemical technique measuring the metabolism of catecholamines. This technique was used to determine the influence of low doses of clonidine (starting from 2 micrograms/kg i.v.) on the activity of the catecholaminergic neurons of the nucleus reticularis lateralis region, site of its hypotensive action, and of the locus ceruleus, which is involved in its sedative effect. There was a correlation between the hypotensive effect of low doses of clonidine (2, 5 and 10 micrograms/kg i.v.) and the decrease of the neuronal metabolic activity within the ventrolateral medulla, whereas only higher doses of clonidine (50 micrograms/kg i.v.) decreased the metabolic activity in the locus ceruleus. Thus, we demonstrate in vivo differences in sensitivity toward the same drug of two different neuronal structures that are involved in the regulation of the cardiovascular and wakefulness functions, respectively. The present study also shows that clonidine has a preferential action on a medulla oblongata region that contains imidazoline-preferring receptors, namely the nucleus reticularis lateralis region, rather than on the locus ceruleus region, that contains mainly alpha-2 adrenoceptors.
Tibirica
E
E
Laboratoire de Pharmacologie Cardiovasculaire et Rénale, Faculté de Médecine, Université Louis Pasteur, Strasbourg, France.
Mermet
C
C
Feldman
J
J
Gonon
F
F
Bousquet
P
P
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002395:Catecholamines / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D008125:Locus Coeruleus / Q000187:drug effects; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*
D002395:Catecholamines; D011941:Receptors, Adrenergic; D015102:3,4-Dihydroxyphenylacetic Acid; D003000:Clonidine