CEREBRAL CATECHOLAMINE DEPLETION IN MICE WITHDRAWN FROM REPEATED MORPHINE TREATMENT AND DEVELOPMENT OF TOLERANCE TO THE ENHANCING EFFECT OF MORPHINE ON NORADRENALINE DEPLETION

The effect of repeated morphine administration on the alpha-methyl-rho-tyrosine (alphaMrhoT)-induced depletion of catecholamines was investigated in various brain areas of mice withdrawn for 1, 2, 3 and 7 days from 5-day morphine treatment. In addition, to clarify the development of tolerance, the effect of acute morphine administration on alphaMrhoT-induced depletion of catecholamines was studied in these selected brain areas of mice withdrawn from repeated morphine treatment. Dopamine depletion was significantly (P < .01) retarded in the striatum and ''rest of forebrain + midbrain' of mice withdrawn for 1 day from morphine treatment. Withdrawal from morphine treatment did not alter alphaMrhoT-induced noradrenaline depletion in the lower brain stem, rest of forebrain + midbrain or hypothalamus. The 10-mg/kg test dose of morphine significantly enhanced alphaMrhoT-induced dopamine depletion in the rest of forebrain + midbrain of control mice withdrawn for 2 days, but did not clearly enhance it in mice withdrawn from morphine. The test dose significantly enhanced noradrenaline depletion in all selected brain areas of control mice withdrawn for 1 to 3 days from saline, but tolerance to the test dose developed in morphine-withdrawn mice. These results suggest that dopamine depletion is retarded in the striatum and rest of forebrain + midbrain of mice withdrawn for 1 day from repeated morphine treatment. However, noradrenaline depletion remains unchanged in all selected brain areas of mice withdrawn from morphine, and tolerance develops to the enhancing effect of morphine on the depletion of noradrenaline in mice withdrawn for 1 to 2 days from morphine.