SUPRASPINAL AND SPINAL POTENCY OF SELECTIVE OPIOID AGONISTS IN THE MOUSE WRITHING TEST

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  • 1 March 1987
    • journal article
    • research article
    • Vol. 240  (3) , 890-894
Abstract
Three agonists with the highest degree of selectivity available for mu ([D-Ala2, NMePhe4,Gly-ol]enkephalin, DAGO), delta ([D-Pen2, D-Pen5]enkephalin, DPDPE) and kappa (U-50,488H, U50) opioid receptors were compared for their activity in inhibiting acetic acid-induced writhing in mice. Additionally, three reference agonists for mu (morphine), delta ([D-Ala2, D-Leu5]enkephalin, DA-DLE) and kappa(ketocyclazocine, KC) receptors were also studied in this test. The agonists were given directly into the lateral cerebral ventricle (i.c.v.) or into the lumbar spinal subarachnoid space (intrathecal), and the potency of each compound was compared across injection sites and with data previously obtained in a thermal analgesic test (mouse hot-plate test). The rank order of potency for inhibition of writhing after i.c.v. administration was DAGO > DADLE > morphine > DPDPE; KC and U50 showed no significant activity by this route. After intrathecal administration, the compounds inhibited writhing with a rank administration, the compounds inhibited writhing with a rank potency order of DAGO > KC > morphine = DADLE > DPDPE > U50. All compounds were more potent in inhibiting writhing at spinal sites than at supraspinal sites; DPDPE and DAGO were 15 and 24 times more potent after intrathecal than after i.c.v. administration, respectively. The proposed delta agonists DPDPE and DADLE inhibited writhing at both spinal and supraspinal sites. Further, although the proposed kappa-acting compounds KC and U50 were effective at relatively low doses at spinal levels, these compounds lacked activity at superaspinal sites at doses not causing sedation. The rank order of potency of KC and U50 against a chemically induced nociceptive stimulus differs dramatically from that previously reported in the hot-plate test. Our results suggest the involvement of distinct opioid receptors (kappa receptors) that may be involved in the modulation of chemically induced nociception (but not thermal nociception) at spinal but not supraspinal levels. Other opioid receptor types may modulate both thermal and chemical nociception at spinal and supraspinal sites.