Differences in the effects of morphine on the alpha-methyl-p-tyrosine-induced depletion of dopamine and noradrenaline in various areas of the mouse brain.
The effect of morphine on the alpha-methyl-p-tyrosine (alpha MT)-induced depletion of dopamine (DA) and noradrenaline (NA) was studied in various brain areas of male NMRI mice, whose locomotor activity is clearly stimulated by morphine. Morphine (10 mg/kg) accelerated the alpha MT-induced DA depletion in the striatum and in the area "rest of forebrain + midbrain", which contains the limbic dopaminergic neurons, but did not clearly alter it in the hypothalamus. The effects were blocked by naloxone. The enhancement of the striatal DA depletion was attenuated when morphine was given after alpha MT or when morphine dose was increased to 30 mg/kg. The smallest dose of morphine to enhance the alpha MT-induced NA depletion in the forebrain + midbrain area was 3 mg/kg, and in the hypothalamus and the lower brain stem 10 mg/kg. The enhancement of the NA depletion was dose-dependent, occurred whether morphine was given before or after alpha MT, and was blocked by naloxone. Our findings suggest that morphine alters the alpha MT-induced depletion of cerebral DA in mice similarly to what has been reported to occur in rats. In contrast its effects on cerebral NA depletion in mice are clearly different from its effects in rats. The substantial activation of cerebral noradrenergic systems, especially of those in the forebrain + midbrain area, in mice could underly the fact that morphine's predominant behavioural effect in mice is stimulation of motor activity.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology*; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009292:Narcotic Antagonists; D009638:Norepinephrine / Q000378:metabolism; D019805:alpha-Methyltyrosine
D002395:Catecholamines; D008781:Methyltyrosines; D009292:Narcotic Antagonists; D019805:alpha-Methyltyrosine; D009020:Morphine; D004298:Dopamine; D009638:Norepinephrine