Abstract

Inhibition of the electrically induced contractions of the guinea-pig ileum has been shown to be a reliable index of the relative potency of various narcotic analgesics. This property suggests that this preparation might be useful in attempts to elucidate the mechanism by which morphine induces analgesia in the central nervous system. In light of the inhibitory effects of 5-hydroxytryptamine (5-HT) on the ileum and its interactions with morphine in other tissues, the effect of 5-HT on the inhibitory response of the ileum to morphine was studied. Concentrations of 5-HT ranging from 2 x 10^-8 to 2 x 10^-7 M can potentiate the inhibitory effects of morphine, and vice versa; small concentrations of morphine (10^-5 M) can potentiate the inhibitory response to 5-HT. Both of these effects can be abolished by washing. This potentiation is also observed with both nalorphine and methadone and seems to be due to a specific interaction between 5-HT and narcotic analgesics. Similar concentrations of 5-HT have no effect on the inhibition produced by norepinephrine, and norepinephrine itself has no effect on the inhibition produced by morphine. Lysergic acid diethylamide (0.1 µg/ml) can antagonize the inhibitory effects of 5-HT but can also produce a marked potentiation of the response to morphine. The above suggests that 5-HT may play an essential role in the mechanism by which morphine induces analgesia in the central nervous system.