Modulation of p-mediated antinociception by agonists in the mouse: selective potentiation of morphine and normorphine by [D-Pen2,D-Pen s ]enkephalin

The effect of the &selective agonist [D-Pen2,D-PenS]enkephalin (DPDPE) on the antinociception produced by intracerebroventricular (i.c.v.) administration of the # agonists morphine, [D-Ala2,NMePhe4,Gly-olS]enkephalin (DAGO), [NMePhe3,D-Proa]morphiceptin (PLO17), fl-endorphin, phenazocine, etorphine and sufentanil was studied in mice. Only the antinociceptive effects of morphine and normorphine were modulated by i.c.v, coadministration of a dose of DPDPE which did not produce any significant antinociception alone. Both the morphine and normorphine dose-response lines were displaced to the left in the presence of DPDPE. The 8-selective antagonist ICI174,864 (N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH) (where Aib is a-aminoisobutyric acid) blocked the modulation of morphine antinociception by DPDPE. ICI 174,864 alone failed to produce either a significant increase or decrease of morphine, phenazocine, etorphine or fl-endorphin antinociception. The results of the present study provide support for the hypothesis that the enkephalins may function to modulate antinociception produced at the /~ receptor; such modulation may come about via the existence of an opioid #-~ receptor complex. The/~ receptors existing in such a complex may be selectively activated by morphine and normorphine, but not the other/~ agonists studied here. Thus, the enkephalins may function both to directly initiate, as well as to modulate, some forms of supraspinal receptor-mediated antinociception.