Effects of acute morphine administration on noradrenaline turnover and metabolism in various brain parts of control and handled rats.
The main purpose of these experiments was to study whether the morphine-induced changes in cerebral noradrenaline (NA) turnover differ between various brain areas of male Wistar rats assessed by the alpha-methyl-p-tyrosine (alpha MT)-induced NA depletion. The effects of repeated saline injections (20 days) on the morphine-induced changes in NA and also in free and sulphated 3-methoxy-4-hydroxyphenylethylene glycol (MOPEG) concentrations were studied. 5 to 40 mg/kg of morphine reduced the alpha MT-induced NA depletion in the cortical hemispheres, while 40 mg/kg of morphine enhanced it in the lower brain stem. 10 mg/kg of morphine lowered the NA concentration in limbic forebrain and hypothalamus and increased it in the cortical areas. It also elevated the MOPEG concentrations in all brain parts with the sole exception of sulphated MOPEG in the cortical hemispheres. Naltrexone antagonized the morphine-induced changes in NA turnover and MOPEG concentrations. The only significant handling-induced change was the elevation of NA concentrations in the hypothalamus. The increasing effect of morphine on the sulphated MOPEG concentration in the prefrontal cortex and the lower brain stem was attenuated in handled rats. In conclusion, these findings show that, the response of cortical NA neurones to acute morphine administration is retardation of turnover rather than activation which occurs most notably in the lower brain stem. Furthermore, the responses are modified by previous exposure of rats to handling.
Department of Pharmacy, University of Helsinki, Finland.
L M
LM
Attila
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013312:Stress, Physiological / Q000378:metabolism*
C030284:3-methoxy-4-hydroxyphenylglycol sulfate; D008734:Methoxyhydroxyphenylglycol; D009271:Naltrexone; D009020:Morphine; D009638:Norepinephrine