Functional and autoradiographic studies to locate the sites at which clonidine acts to cause hyperglycaemia and inhibition of opiate-induced sympathetic outflow.
The effect of intracisternal administration of clonidine (1 microgram/kg) on the response to intravenous injection of morphine (4 mg/kg) was examined in conscious rabbits. Morphine acts on central opiate receptors to increase sympathetic outflow and cause hypertension. Clonidine, given intracisternally, prevented the morphine-induced rise in mean arterial pressure, fall in heart rate and increase in catecholamines in plasma. Using in vitro autoradiography, alpha 2-adrenoceptors were localised in the nucleus of the tractus solitarius and the dorsal motor nucleus of the vagus and these may be two of the sites at which clonidine acts. Clonidine also causes hyperglycaemia after intravenous administration and the site of action was investigated by comparing the effects of intravenous and intracerebroventricular administration of clonidine (1, 2 and 2 micrograms/kg), given at intervals of 30 min. Similar increases in glucose occurred after intraventricular and intravenous administration of clonidine, indicating that it has both central and peripheral actions, which increase glucose by different mechanisms. Clonidine, given intraventricularly also reduced mean arterial pressure and heart rate but there were no effects after intravenous administration. These studies demonstrate that the inhibitory effect of clonidine on opiate-induced stimulation of sympatho-adrenal outflow is central, whereas the hyperglycaemic effect of clonidine depends on both central and peripheral mechanisms.
May
C N
CN
Department of Medicine, St Mary's Hospital Medical School, London, U.K.
Dashwood
M R
MR
Whitehead
C J
CJ
Mathias
C J
CJ
D000818:Animals; D001345:Autoradiography; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001798:Blood Proteins / Q000378:metabolism; D002946:Cisterna Magna; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006943:Hyperglycemia / Q000097:blood / Q000139:chemically induced*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000187:drug effects*
D001786:Blood Glucose; D001798:Blood Proteins; D009294:Narcotics; D009020:Morphine; D003000:Clonidine