Clonidine attenuates increased brain glucose metabolism during naloxone-precipitated morphine withdrawal.
The effect of two doses of clonidine on regional cerebral metabolic rates for glucose were measured during morphine withdrawal in rats. In the first study, 0 or 200 micrograms/kg clonidine was administered to rats subjected to naloxone-precipitated morphine withdrawal (naloxone, 0.5 mg/kg, s.c.), and to non-dependent control rats. In a second study of similar design, 0 or 20 micrograms/kg clonidine were administered. Withdrawal signs in rats subjected to naloxone-precipitated morphine withdrawal and receiving 0, 20 or 200 micrograms/kg clonidine were also assessed. Naloxone-precipitated morphine withdrawal stimulated regional cerebral metabolic rates for glucose (59 of 83 regions in study no. 1; 73 of 83 regions in study no. 2). At 200 micrograms/kg, clonidine attenuated this effect (33 of 59 regions). Although 200 micrograms/kg clonidine directly suppressed regional cerebral metabolic rates for glucose in many regions (significant main effect of clonidine), it attenuated the naloxone-precipitated morphine withdrawal effect specifically in the lateral septal nucleus, medial habenula, subiculum and gracile nucleus (significant interactions between clonidine and morphine withdrawal). The 20 micrograms/kg dose of clonidine had no statistically significant effect. In behavioral experiments, both doses of clonidine diminished withdrawal in that there was no diarrhea, fewer wet-dog shakes and less abnormal posturing. However, locomotion, grooming and jumping were increased by clonidine. Most of these effects were statistically significant only with the 200 micrograms/kg dose. The results of these studies show that clonidine reduces morphine withdrawal-induced increases in regional cerebral metabolic rates for glucose in many brain regions, irrespective of the distribution of alpha 2-adrenoceptors. Although clonidine has been thought to ameliorate morphine withdrawal by actions primarily at the locus coeruleus and central amygdala, it may play a major role in other regions as well.
Kimes
A S
AS
Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224.
Bell
J A
JA
London
E D
ED
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology*; D003837:Deoxy Sugars / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D009270:Naloxone / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D003837:Deoxy Sugars; D009270:Naloxone; D009020:Morphine; D003847:Deoxyglucose; D003000:Clonidine