Biochemical evidence that brainstem adrenaline-containing neurons are activated during clonidine withdrawal in the spontaneously hypertensive rat.
We have investigated the effects of prolonged treatment with clonidine (delivered intravenously via osmotic minipumps, 0.1 mg/kg/day for 7 or 10 days) and of withdrawal of such treatment on brainstem noradrenaline and adrenaline metabolism in the adult spontaneously hypertensive rat (SHR). After a seven day treatment with clonidine, noradrenaline and adrenaline turnovers were unchanged both in the A2-C2 and A1-C1 regions. During withdrawal, the noradrenaline turnover was also unchanged in these regions. However, the adrenaline turnover was significantly increased 16 h after withdrawal (p less than 0.01) in the A2-C2 region and 16 h (p less than 0.01) and 40 h (p less than 0.05) after withdrawal in the A1-C1 region. These results show that noradrenaline metabolism is unchanged both during clonidine treatment and during its withdrawal in the brainstem catecholaminergic regions analyzed. In contrast, the increases in adrenaline turnover found in the A2-C2 and A1-C1 regions suggest that the adrenergic neurons of the brainstem could be activated during clonidine withdrawal. As the adrenergic C1 neurons are a key element of the sympathetic vasopressor system, the increase in adrenaline turnover observed during withdrawal could be at the origin of the sympathetic hyperactivity found after cessation of prolonged treatment with clonidine.
Lambás-Señas
L
L
Laboratoire de Neuropharmacologie-CNRS, Faculté de Pharmacie, Université Claude Bernard, Lyon, France.
Atkinson
J
J
Fluckiger
J P
JP
Sonnay
M
M
Chamba
G
G
Renaud
B
B
D000818:Animals; D001933:Brain Stem / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D003000:Clonidine / Q000009:adverse effects / Q000494:pharmacology*; D004837:Epinephrine / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D013375:Substance Withdrawal Syndrome
D003000:Clonidine; D009638:Norepinephrine; D004837:Epinephrine