Autoradiographic evidence for decrease in binding of mu- and delta-opioid receptors after subchronic [D-Ala2,D-Leu5]enkephalin treatment in rats.
Tolerance to the antinociceptive effect of [D-Ala2,D-Leu5]enkephalin (DADLE) developed in Sprague-Dawley rats given the peptide chronically. delta-Opioid receptor binding is significantly reduced in P2 membranes from various brain areas after 1-3 days' treatment. mu-Opioid receptor binding, however, is reduced only in striatum, and only after 5 days. To study this finding further, receptor autoradiography was used to quantify mu- and delta-opioid binding sites in rat brain sections after subchronic DADLE treatment. Autoradiograms were made following equilibrium binding of the highly selective opioid radioligands, [3H]Tyr-D-Ala-Gly-MePhe-Gly-ol ([3H]DAMGO) and [3H][D-Pen2,5]enkephalin ([3H]DPDPE) to brain sections. Computerized grain counting was applied to discrete regions of the autoradiograms corresponding to caudate and interpeduncular nuclei. We found that [3H]DAMGO binding decreased in caudate after 3 days of DADLE treatment and [3H]DPDPE binding decreased in the interpeduncular nucleus, rostral portion, after 1-day DADLE treatment. These autoradiographic changes are consistent with our earlier results for biochemical binding, although we now detected an earlier change in mu-opioid receptor binding, by using autoradiography.
Tao
P L
PL
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan.
Seybold
V S
VS
Loh
H H
HH
D000595:Amino Acid Sequence; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D002421:Caudate Nucleus / Q000033:anatomy & histology / Q000378:metabolism; D004361:Drug Tolerance; D020881:Enkephalin, D-Penicillamine (2,5)-; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology*; D004745:Enkephalins / Q000494:pharmacology; D008024:Ligands; D008297:Male; D008636:Mesencephalon / Q000033:anatomy & histology / Q000378:metabolism; D008969:Molecular Sequence Data; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*
D000700:Analgesics; D004745:Enkephalins; D008024:Ligands; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D016308:Enkephalin, Leucine-2-Alanine; D020881:Enkephalin, D-Penicillamine (2,5)-