The fall of homovanillic acid and 5-hydroxyindoleacetic acid concentrations in brains of mice withdrawn from repeated morphine treatment and their restoration by acute morphine administration.

The striatal homovanillic acid (HVA) and cerebral 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were estimated in male mice withdrawn from 3- to 5-day morphine treatment (total dose: 1,100-2,350 mg/kg). All mice were given probenecid (200 mg/kg, 2 hours). The HVA concentration was decreased (by 26%) in mice withdrawn from 3-day treatment, but the 5-HIAA concentration fell (by 22%) only after 4-day treatment. An acute morphine dose (30 mg/kg, 2 hours) clearly elevated the HVA concentration in mice withdrawn from 4-day treatment, but mice withdrawn from 3-day treatment tended to be tolerant to the HVA concentration elevating effect of morphine. The acute dose increased the 5-HIAA concentration in mice withdrawn from 4-day treatment, by 20-40%, but the mice withdrawn from 3-day treatment were clearly tolerant to this effect of morphine. These results suggest that endogenous activities of dopaminergic and 5-HTergic neurons are attenuated by repeated morphine treatment. However, such attenuation seems to reactivate these neurons to respond to acute morphine administration nearly normally.