Noradrenaline release in rat locus coeruleus is regulated by both opioid and alpha(2) -adrenoceptors.
Extracellular fluid levels of noradrenaline (NA) in the locus coeruleus (LC) during naloxone-precipitated morphine withdrawal with pretreatment of yohimbine (1 mg kg (-1), s.c.) or clonidine (1 mg kg (-1), s.c.) were measured in rats. There was a significant increase in the NA level after the injection of naloxone (2 mg kg (-1), i.p.) in the morphine-dependent rats. Moreover, the NA levels in the LC markedly increased during the 30-60 min following the naloxone (i.p.) challenge in the morphine-dependent rats pretreated with yohimbine. In contrast, the naloxone challenge in morphine-dependent rats pretreated with clonidine notably decreased the levels of NA in the LC. Behavioral signs of withdrawal were observed following the naloxone challenge in the morphine-dependent rats pretreated with yohimbine, with minimal signs in the morphine-infused rats pretreated with clonidine, and none in the saline-infused controls. These results directly suggest that NA increased within the LC after the naloxone challenge in morphine-dependent animals pretreated with yohimbine may be, at least in part, regulated by alpha(2) -adrenoceptors in the LC.
Department of Clinical Pharmacology, Hokkaido College of Pharmacy, 7-1 Katsuraoka-cho, Otaru, Hokkaido 047-02, Japan.
Tohru
T
Nakai
Masahiro
M
Hayashi
Kazuo
K
Ichihara
Hiroyuki
H
Wakabayashi
Katsuji
K
Hoshi
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D007276:Injections, Intraventricular; D008125:Locus Coeruleus / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009020:Morphine / Q000009:adverse effects; D009021:Morphine Dependence / Q000523:psychology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000009:adverse effects; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000523:psychology; D015016:Yohimbine / Q000494:pharmacology
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D009292:Narcotic Antagonists; D009294:Narcotics; D018341:Receptors, Adrenergic, alpha-2; D011957:Receptors, Opioid; D015016:Yohimbine; D009270:Naloxone; D009020:Morphine; D003000:Clonidine; D009638:Norepinephrine