Cerebral dopamine and noradrenaline turnover and effects of morphine test dose in rats withdrawn from 20 days' morphine treatment.

Depletion of dopamine (DA) and noradrenaline (NA) induced by alpha-methyl-p-tyrosine (alpha MT) was studied in five different brain areas of rats withdrawn from 20 days' chronic treatment for 0.5, 1, 2, 3, 4 or 6 days. Some of the alpha MT-treated rats were given a challenge dose of morphine (10 mg/kg) 2.5 h before decapitation. The depletion of DA was clearly retarded in the limbic forebrain but not in the striatum of rats withdrawn from morphine for 1 and 2 days, whereas the alpha MT-induced NA depletion was slightly accelerated in the hemispheres but not in any other part of the brain of rats withdrawn for 1 day. The morphine challenge dose accelerated DA depletion slightly more in limbic forebrain and striatum of chronic morphine rats than of control rats. The challenge dose clearly retarded the NA depletion in all brain parts in rats withdrawn from morphine for 1 and 2 days. This retardation was most pronounced in the hemispheres. In control rats, too, the challenge dose tended to retard the NA depletion in the hemispheres although it enhanced it in the lower brain stem. Our results suggest that the DA neurons in the limbic forebrain and NA neurons in the hemispheres are the catecholamine neurons most readily affected by chronic morphine treatment. In both groups of neurons the alterations were clearest when withdrawal-induced weight loss was most evident.