Tolerance to diacetyl morphine antinociception: effects on brain serotonin

The effects of 5 mg kg-1 diacetyl morphine (DAM) on brain serotonin metabolism of rats were investigated following tolerance to the antinociceptive effects of 2.5 mg kg-1 DAM. Brain levels of tryptophan and 5-hydroxy indoleacetic acid (5-HIAA) were higher in the DAM-tolerant rats killed 24 h after last daily administration of 2.5 mg kg-1 DAM. Administration of 5 mg kg-1 DAM produced less antinociception in DAM-tolerant than DAM-naive rats and increased brain tryptophan concentration in both tolerant and naive rats. 5-HIAA concentrations increased only in naive rats. Combined use of drugs interfering with brain 5-HT turnover along with opiates may be of future benefit for the treatment of chronic pain.