CHARACTERIZATION OF SUPRASPINAL ANTINOCICEPTIVE ACTIONS OF OPIOID DELTA-AGONISTS IN THE RAT

Supraspinally mediated antinociception has been clearly established fo r agonists acting via both mu- and delta-opioid receptors. The present experiments were undertaken to further characterize the role of supra spinal opioid delta receptors in the mediation of antinociception in r ats and to examine the possible role of putative delta(1)- and delta(2 )-opioid receptors in the antinociceptive effect. Cannulae directed at the right lateral ventricle, the periaqueductal gray (FAG), or the me dullary reticular formation (MRF) were implanted in adult male, Spragu e-Dawley rats for the microinjection of [D-Ala(2),Glu(4)]deltorphin (d elta(2) agonist), [D-Pen(2),D-Pen(5)]enkephalin (DPDPE, delta(1) agoni st), [D-Ser(2),Leu(5),Thr(6)]enkephalin (DSLET, mixed delta/mu agonist ) or morphine (reference mu-opioid). Pretreatments (24 h prior to agon ist microinjection) were made with the putative delta(1) and delta(2) antagonists, [D-Ala(2),Leu(5),Cys(6)]enkephalin (DALCE) and [D-Ala(2), Cys(4)]deltorphin (Cys-DELT) and antinociception was measured in the 5 5 degrees C hot plate (HP) and 52 degrees C and 55 degrees C (low and high intensity) warm-water tail-flick (TF) tests. Data were converted to percent maximal possible effect (%MPE). Intracerebroventricular (i. c.v.) administration of DPDPE produced less than a 50% MPE in the HP t est whereas [D-Ala(2),Glu(4)]deltorphin produced Cys-DELT sensitive an tinociception of up to 92% MPE. Neither i.c.v. agonist was effective i n the TF assays, and both agonists were without effect in the FAG. [D- Ala(2),Glu(4)]deltorphin microinjected into the MRF produced Cys-DELT sensitive antinociception of 60 and 47% MPE in the HP and low-intensit y TF tests, respectively, but was not effective in the 55 degrees C TF test; DPDPE did not produce antinociception when microinjected at thi s site. Microinjection of DSLET in the MRF produced significant antino ciception in all three assays. Morphine produced antinociception follo wing i.c.v. administration or microinjection into the FAG in all tests . Microinjection of morphine into the MRF produced antinociception in the HP and 52 degrees C, but not 55 degrees C, TF tests. Morphine anti nociception was not antagonized by either DALCE or Cys-DELT. These dat a demonstrate that supraspinal delta-opioid receptors can be activated to elicit antinociception in the rat and that opioid delta(2) recepto rs predominate in this effect. Further, these effects may occur predom inately via inhibition of supraspinally organized behavior without act ivation of descending systems such as those mediating the TF response in the rat.