Role of mu and delta receptors in the supraspinal and spinal analgesic effects of [D-Pen2, D-Pen5]enkephalin in the mouse.

The opioid receptors involved in the supraspinal and spinal actions of [D-Pen2, D-Pen5]enkephalin (DPDPE) for production and/or modulation of analgesia were investigated in two thermal analgesic tests, the mouse warm water (55 degrees C) tail-withdrawal assay and the radiant heat tail-flick test. Two approaches were used at supraspinal and spinal sites: determination of possible cross-tolerance between morphine and a variety of receptor selective/nonselective agonists (DPDPE, [D-Pen2, L-Pen5]enkephalin (DPLPE), [D-Ala2, MePhe4, Gly-ol]enkephalin, [D-Ala2, Met5]enkephalin amide, [D-Ser2, Leu5, Thr6]enkephalin and [D-Thr2 Leu, Thr6]enkephalin) and possible potentiation of morphine (mu) analgesia by proposed delta agonists (DPDPE, DPLPE and [D-Ala2, D-Leu5]enkephalin) in naive and morphine-tolerant mice. Additionally, proposed mu (morphine) and delta (DPDPE) agonists were evaluated for their i.c.v. analgesic effectiveness in the absence, and in the presence, of the proposed delta antagonist ICI 174,864. The present communication now reports that after i.c.v. administration analgesic cross-tolerance could be demonstrated between morphine and a variety of relatively selective or nonselective opioids but not to the highly delta selective DPDPE and DPLPE. This result was consistent with direct antagonism of i.c.v. DPDPE, but not morphine analgesia, by ICI 174,864. Furthermore, i.c.v. DPDPE and DPLPE were able to potentiate morphine analgesia in either naive or morphine-tolerant mice. In contrast, after intrathecal administration, cross-tolerance could be demonstrated between DPDPE or DPLPE and morphine, and no potentiation of morphine by DPDPE could be observed.(ABSTRACT TRUNCATED AT 250 WORDS)