PMID- 8657428
OWN - NLM
STAT- MEDLINE
DCOM- 19960731
LR  - 20210112
IS  - 0304-3959 (Print)
IS  - 0304-3959 (Linking)
VI  - 62
IP  - 3
DP  - 1995 Sep
TI  - Characterization of supraspinal antinociceptive actions of opioid delta agonists 
      in the rat.
PG  - 287-293
LID - 10.1016/0304-3959(94)00231-3 [doi]
AB  - Supraspinally mediated antinociception has been clearly established for agonists 
      acting via both micro- and delta-opioid receptors. The present experiments were 
      undertaken to further characterize the role of supraspinal opioid delta receptors 
      in the mediation of antinociception in rats and to examine the possible role of 
      putative delta1- and delta2-opioid receptors in the antinociceptive effect. 
      Cannulae directed at the right lateral ventricle, the periaqueductal gray (PAG), 
      or the medullary reticular formation (MRF) were implanted in adult male, 
      Sprague-Dawley rats for the microinjection of [D-Ala2,Glu4]deltorphin (delta2 
      agonist), [D-Pen2,D-Pen5]enkephalin (DPDPE, delta1 agonist), 
      [D-Ser2,Leu5,Thr6]enkephalin (DSLET, mixed delta/micro agonist) or morphine 
      (reference micro-opioid). Pretreatments (24 h prior to agonist microinjection) 
      were made with the putative delta1 and delta2 antagonists, 
      [D-Ala2,Leu5,Cys6]enkephalin (DALCE) and [D-Ala2,Cys4]deltorphin (Cys-DELT) and 
      antinociception was measured in the 55 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 test 
      whereas [d-Ala2,Glu4]deltorphin produced Cys-DELT sensitive antinociception of up 
      to 92% MPE. Neither i.c.v. agonist was effective in the TF assays, and both 
      agonists were without effect in the PAG. [D-Ala2,Glu4]deltorphin microinjected 
      into the MRF produced Cys-DELT sensitive antinociception of 60 and 47% MPE in the 
      HP and low-intensity TF tests, respectively, but was not effective in the 55 
      degrees C TF test; DPDPE did not produce antinociception when microinjected at 
      this site. Microinjection of DSLET in the MRF produced significant 
      antinociception in all three assays. Morphine produced antinociception following 
      i.c.v. administration or microinjection into the PAG 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 anticociception was not antagonized by 
      either DALCE or Cys-DELT. These data demonstrate that supraspinal delta-opioid 
      receptors can be activated to elicit antinociception in the rat and that opioid 
      delta2 receptors predominate in this effect. Further, these effects may occur 
      predominately via inhibition of supraspinally organized behavior without 
      activation of descending systems such as those mediating the TF response in the 
      rat.
FAU - Ossipov, Michael H
AU  - Ossipov MH
AD  - Departments of Pharmacology and Chemistry, University of Arizona Health Sciences 
      Center, Tucson, AZ 85724 USA.
FAU - Kovelowski, Carl J
AU  - Kovelowski CJ
FAU - Nichols, Michael L
AU  - Nichols ML
FAU - Hruby, Victor J
AU  - Hruby VJ
FAU - Porreca, Frank
AU  - Porreca F
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Pain
JT  - Pain
JID - 7508686
RN  - 0 (Enkephalins)
RN  - 0 (Oligopeptides)
RN  - 0 (Receptors, Opioid, delta)
RN  - 0 (deltorphin, Ala(2)-Cys(4)-)
RN  - 110881-59-9 (enkephalin-Leu, Ala(2)-Cys(6)-)
RN  - 58822-25-6 (Enkephalin, Leucine)
RN  - 63631-40-3 (Enkephalin, Leucine-2-Alanine)
RN  - 75644-90-5 (enkephalin, Ser(2), Leu(5), Thr(6)-)
RN  - 76I7G6D29C (Morphine)
RN  - 88373-73-3 (Enkephalin, D-Penicillamine (2,5)-)
SB  - IM
MH  - Animals
MH  - Cerebral Ventricles/*drug effects
MH  - Enkephalin, D-Penicillamine (2,5)-
MH  - Enkephalin, Leucine/analogs & derivatives/pharmacology
MH  - Enkephalin, Leucine-2-Alanine/analogs & derivatives/pharmacology
MH  - Enkephalins/pharmacology
MH  - Hot Temperature
MH  - Injections, Intraventricular
MH  - Male
MH  - Medulla Oblongata
MH  - Morphine/pharmacology
MH  - Nociceptors/*drug effects
MH  - Oligopeptides/pharmacology
MH  - Pain Measurement
MH  - Periaqueductal Gray/*drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Opioid, delta/*agonists/antagonists & inhibitors
MH  - Reticular Formation/*drug effects
EDAT- 1995/09/01 00:00
MHDA- 1995/09/01 00:01
CRDT- 1995/09/01 00:00
PHST- 1995/09/01 00:00 [pubmed]
PHST- 1995/09/01 00:01 [medline]
PHST- 1995/09/01 00:00 [entrez]
AID - 00006396-199509000-00004 [pii]
AID - 10.1016/0304-3959(94)00231-3 [doi]
PST - ppublish
SO  - Pain. 1995 Sep;62(3):287-293. doi: 10.1016/0304-3959(94)00231-3.