Opioid and substance P receptor adaptations in the rat spinal cord following sub-chronic intrathecal treatment with morphine and naloxone.
The effect of continuous intrathecal infusion with morphine (5 mu/h) or naloxone (2 micrograms/h) was investigated with regard to analgesia and the apparent density of mu- and delta-opioid and neurokinin-I/substance P receptors in the rat spinal cord. Morphine infusion increased tail-flick and paw-pressure responses until day 4 after the mini-osmotic pump implant. A decline in antinociception, reflecting tolerance to morphine, was then apparent in both tests. Quantitative in vitro receptor autoradiography of [125I]FK-33824, [125I][D.Ala2]deltorphin-I and [125I] Bolton-Hunter substance P binding sites, as ligands of mu, delta and neurokinin-I/substance P receptors, respectively, was performed on lumbosacral spinal cord sections of seven-days tolerant animals. Treatments with morphine and naloxone induced a similar increase (37%) in the number of delta binding sites in the superficial laminae of the dorsal horn. In contrast, the density of mu-opioid receptors was only affected by naloxone (50% increase). Neurokinin-I/substance P binding parameters were not altered by these treatments. Thus, it appears that delta-opioid binding sites may be of special relevance with regard to the development of tolerance to opiates in the spinal cord.
Gouarderes
C
C
Laboratoire de Pharmacologie et de Toxicologie Fondamentales, C.N.R.S., Toulouse, France.
Jhamandas
K
K
Cridland
R
R
Cros
J
J
Quirion
R
R
Zajac
J M
JM
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin / Q000378:metabolism; D003720:Densitometry; D004361:Drug Tolerance; D066298:In Vitro Techniques; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology*; D009842:Oligopeptides / Q000378:metabolism; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D011957:Receptors, Opioid / Q000187:drug effects*; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000187:drug effects; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism; D013388:Succinimides / Q000378:metabolism
D000700:Analgesics; C043194:Bolton Hunter reagent-substance P conjugate; D009842:Oligopeptides; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D013388:Succinimides; C060208:deltorphin I, Ala(2)-; D013373:Substance P; D009270:Naloxone; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; D009020:Morphine