Lack of antinociceptive cross-tolerance between intracerebroventricularly administered beta-endorphin and morphine or DPDPE in mice.
Antinociceptive tolerance and cross-tolerance to intracerebroventricular (i.c.v.) beta-endorphin, morphine, and DPDPE (D-Pen2-D-Pen5-enkephalin) induced by a prior i.c.v. administration of beta-endorphin, morphine and DPDPE, respectively, were studied in mice. Acute tolerance was induced by i.c.v. pretreatment with beta-endorphin (0.58 nmol), morphine (6 nmol) and DPDPE (31 nmol) for 120, 180 and 75 min, respectively. Various doses of beta-endorphin, morphine or DPDPE were then injected. The tail-flick and hot-plate tests were used as antinociceptive tests. Pretreatment of mice with beta-endorphin i.c.v. reduced inhibition of the tail-flick and hot-plate responses to i.c.v. administered beta-endorphin, but not morphine and DPDPE. Pretreatment of mice with morphine i.c.v. reduced inhibition of the tail-flick and hot-plate responses to morphine but not beta-endorphin. Pretreatment of mice with DPDPE reduced inhibition of the tail-flick and hot-plate responses to DPDPE but not beta-endorphin. The results indicate that one injection of beta-endorphin, morphine or DPDPE induces acute antinociceptive tolerance to its own distinctive opioid receptor and does not induce cross-tolerance to other opioid agonists with different opioid receptor specificities. The data support the hypothesis that beta-endorphin, morphine and DPDPE produce antinociception by stimulating specific epsilon, mu- and delta-opioid receptors, respectively.
Suh
H H
HH
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee.
Tseng
L F
LF
D000700:Analgesics; D000818:Animals; D001921:Brain / Q000187:drug effects*; D003429:Cross Reactions; D004361:Drug Tolerance; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects; D001615:beta-Endorphin / Q000494:pharmacology*
D000700:Analgesics; D004745:Enkephalins; D011957:Receptors, Opioid; D001615:beta-Endorphin; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-