Effect of morphine on the cerebral contents of metabolites of dopamine in normal and tolerant mice: its possible relation to analgesic action.

1. The administration of an analgesic dose (10 mg/kg, s.c.) of morphine increased the concentrations of the dopamine metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the brains of normal mice, and the time course of the change in the DOPAC concentration corresponded approximately to that of morphine analgesia. The increase in the concentration of the DOPAC induced by morphine (20 mg/kg, s.c.) was completely suppressed by nalorphine (2 mg/kg, s.c.) given 5 min after the morphine administration.2. In morphine-tolerant mice the concentrations of DOPAC and HVA in the brain did not differ from those observed in normal mice, and the increase in the concentrations of DOPAC and HVA in brain after the acute administration of morphine no longer occurred.3. Nalorphine (2 mg/kg) given alone did not cause any change in brain DOPAC and HVA concentrations in normal mice.4. The morphine-induced increase in DOPAC and HVA concentrations in the brain are discussed in the light of the hypothesis that dopamine might participate not only in the extrapyramidal motor system but also in the sensory mechanisms of the brain.