Involvement of 5-hydroxytryptamine in the analgesic action of pethidine and morphine in mice

1 Groups of mice were pretreated with the 5-hydroxytryptamine (5-HT) depletors, fenfluramine or p-chlorophenylalanine (PCPA), followed by pethidine or morphine. 2 Fenfluramine alone produced a short lasting analgesia but PCPA was without any effect. 3 Pethidine and morphine both increased hot plate reaction times measured after 30 min. 4 Pretreatment with PCPA attenuated morphine analgesia but did not affect pethidine analgesia. Fenfluramine did not alter the response to either analgesic. 5 PCPA produced a significant depletion of brain 5-HT levels which was not reversed by the analgesics. The fenfluramine-induced decrease in 5-HT was reversed by morphine but not by pethidine. 6 The results support the involvement of 5-HT in the antinociceptive action of morphine in the mouse.