Mouse brain catecholamines, 5-hydroxytryptamine and the antinociceptive activity of pethidine

The involvement of brain 5-hydroxytryptamine (5-HT), noradrenaline and dopamine in the antinociceptive activities of pethidine and morphine has been compared in the mouse. Differences have been shown in the activities of pethidine and morphine in mice treated with either 5-hydroxytryptophan or reserpine. No differences between the activities of pethidine and morphine were demonstrated in mice treated with either alpha-methyl-p-tyrosine, L-dopa or p-chlorophenylalanine. In reserpinised mice, pethidine's antinociceptive activity was either potentiated, unaffected or antagonised, dependent upon the reserpine dose schedule. Pethidine was shown to be able to raise brain 5-HT concentrations in reserpinised mice. This effect was also dependent upon the reserpine dose schedule used. Morphine, which was antagonised by all reserpine dose schedules, did not raise noradrenaline or dopamine in control or reserpinised mice. Although the reserpine schedule, which potentiated pethidine's antinociceptive activity, was the same as that in which pethidine had the most marked effects upon 5-HT, no definite connections between the two observations could be made. Naloxone abolished the antinociceptive activity of pethidine in reserpinised mice, but not the rise in 5-HT.