Catecholamine utilization in distinct mouse brain nuclei during acute morphine treatment, morphine tolerance and...

The steady-state levels and utilization (alpha-MPT-induced disappearance) of noradrenaline (NA) and dopamine (DA) were measured in distinct mouse brain nuclei after acute morphine challenge, in mice rendered tolerant to morphine, and during the naloxone-precipitated morphine withdrawal syndrome. Mouse brain nuclei containing mainly the cell body areas and some terminal projections of major NA- and DA-containing pathways were selected (nucleus tractus solitarii, locus coeruleus, substantia nigra, area tegmentalis ventralis and nucleus caudatus, nucleus accumbens, gyrus dentatus hippocampi, nucleus raphe dorsalis respectively). Acute morphine treatment reduced the utilization of NA in all brain nuclei but the substantia nigra. In morphine-tolerant mice, all changes characteristic for acute morphine treatment disappeared. Instead, an increased NA utilization was observed in the nucleus tractus solitarii and the area tegmentalis ventralis in the tolerant animals. During morphine withdrawal, an abrupt decrease was observed in the utilization of NA in the nucleus tractus solitarii, whereas the NA utilization in the gyrus dentatus abruptly increased, as compared to the tolerant state. Acute morphine challenge decreased the utilization of DA in the nucleus caudatus, locus coeruleus and nucleus raphe dorsalis. In the tolerant mouse, an increased utilization of DA was observed in the nucleus tractus solitarii. During morphine withdrawal, DA utilization was decreased in the substantia nigra and the area tegmentalis ventralis, while in the nucleus accumbens withdrawal resulted in an increase of DA utilization. The data suggest that acute effects of morphine as well as morphine tolerance/dependence are accompanied by, and likely to be associated with, distinct changes in the catecholamine metabolism of specific mouse brain nuclei.