POSSIBLE REGULATORY ROLE OF DYNORPHIN ON MORPHINE-ENDORPHIN-INDUCED AND BETA-ENDORPHIN-INDUCED ANALGESIA

Abstract

Dynorphin-(1-13), but not dynorphin-(1-9), can significantly inhibit morphine- or .beta.-endorphin-induced analgesia despite not having any appreciable analgesic activity itself. Dynorphin-(1-13) showed no inhibitory effect on FK33824[D-Ala2,MePhe4,Met(05-ol)enkephalin]-induced analgesia. In the present study the effect of dynorphin was studied on morphine-, .beta.-endorphin-, D-ala2-D-leu5-enkephalin- or FK33824-induced analgesia in both naive, morphine-tolerant and morphine-dependent mice. Although dynorphin may inhibit morphine- or .beta.-endorphin-induced analgesia in naive animals, the peptide is not effective in inhibiting D-ala2-D-leu5-enkephalin- or FK33824-induced analgesia. Dynorphin is also effective in blocking spontaneous withdrawal jumping in morphine-dependent animals. Dynorphin-(1-13) may play a modulatory role in regulating analgesia due to morphine or .beta.-endorphin, but not that due to enkephalin. The action of peptides on morphine- or .beta.-endorphin-induced analgesia in the naive state is different from that of the tolerant state, suggesting that dynorphin may be involved in the development of morphine tolerance and physical dependence.