In previous studies, we observed that dynorphin- (1-13), but not dynorphin-(1-9), can significantly inhibit morphine- or β-endorphin-induced analgesia despite not having any appreciable analgesic activity itself. Dynorphin-(1-13) showed no inhibitory effect on Sandoz FK33824-induced analgesia. In the present study, we examined the effect of dynorphin on morphine-, β-endorphin-, D-ala2-D-leu5-enkephalin- or Sandoz FK33824-induced analgesia in both naive, morphine-tolerant and morphine-dependent mice. It was found that although dynorphin may inhibit morphine- or β-endorphin-induced analgesia in naive animals, the peptide is not effective in inhibiting D-ala2-D-leu5-enkephalin- or Sandoz FK33824-induced analgesia. Dynorphin is also effective in blocking spontaneous withdrawal jumping in morphine-dependent animals. It is suggested that dynorphin-(1-13) may play a modulatory role in regulating analgesia due to morphine or β-endorphin, but not that due to enkephalin. The action of peptides on morphine- or β-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.
|Original language||English (US)|
|Number of pages||3|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - 1981|