Clonidine but not nifedipine prevents the release of noradrenaline during naloxone-precipitated opiate withdrawal: an in vivo microdialysis study in the rat.
In this study we have examined whether the alpha 2-adrenoceptor agonist clonidine and the calcium channel antagonist nifedipine firstly inhibit the naloxone-precipitated withdrawal syndrome in morphine-dependent rats and secondly reduce central noradrenaline release during withdrawal. We demonstrate that both clonidine (0.1 mg/kg) and nifedipine (10 mg/kg) attenuate the naloxone-precipitated withdrawal syndrome. Using in vivo microdialysis, we demonstrate that following naloxone the release of noradrenaline, as measured by perfusates from hippocampus, increases 300% in morphine-dependent rats. However, whilst pretreatment with clonidine inhibited this increased noradrenaline release, nifedipine did not. These findings suggest that whilst the action of clonidine in attenuating the morphine withdrawal syndrome may be mediated by decreasing central noradrenaline release, this is not the mechanism by which nifedipine acts.
MRC Unit, Radcliffe Infirmary, Oxford, UK.
P H
PH
Silverstone
C
C
Done
T
T
Sharp
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003000:Clonidine / Q000627:therapeutic use*; D008297:Male; D017551:Microdialysis; D009021:Morphine Dependence / Q000523:psychology; D009270:Naloxone / Q000494:pharmacology*; D009543:Nifedipine / Q000627:therapeutic use*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D015431:Weight Loss / Q000187:drug effects
D009270:Naloxone; D009543:Nifedipine; D003000:Clonidine; D009638:Norepinephrine