Noradrenergic and behavioural effects of naloxone injected in the locus coeruleus of morphine-dependent rats and their control by clonidine.
Naloxone HCl (10 micrograms/0.5 ml) was injected in the locus coeruleus (LC) of morphine-dependent rats and the behavioural manifestations of morphine withdrawal and the cortical levels of 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4) were measured 30 min later. Naloxone precipitated a withdrawal syndrome and raised cortical MHPG-SO4 in animals made dependent by ascending doses of morphine for 11 days. An injection of clonidine intraperitoneally (200 micrograms/kg) or in the LC (5 micrograms/0.5 microliter) blocked most aspects of the withdrawal syndrome except jumping and had no effect on the naloxone-induced rise in cortical MHPG-SO4. The findings confirm the hypothesis that the LC is one of the sites where naloxone and clonidine, respectively, precipitate and reduce the narcotic withdrawal syndrome but argue against a role of noradrenergic neurons originating in the LC and innervating the cortex in the ability of clonidine to suppress some aspects of withdrawal syndrome precipitated by naloxone in morphine-dependent animals.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D008125:Locus Coeruleus / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D009020:Morphine / Q000009:adverse effects; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D009638:Norepinephrine; D051381:Rats; D019966:Substance-Related Disorders / Q000503:physiopathology*
C030284:3-methoxy-4-hydroxyphenylglycol sulfate; D009270:Naloxone; D008734:Methoxyhydroxyphenylglycol; D009020:Morphine; D003000:Clonidine; D009638:Norepinephrine