Lack of antinociceptive cross-tolerance between intracerebroventricularly administered β-endorphin and morphine or DPDPE in mice

Abstract

Antinociceptive tolerance and cross-tolerance to intracerebroventricular (i.c.v.) β-endorphin, morphine, and DPDPE (D-Pen 2-D-Pen 5-enkephalin) induced by a prior i.c.v. administration of β-endorphin, morphine and DPDPE, respectively, were studied in mice. Acute tolerance was induced by i.c.v. pretreatment with β-endorphin (0.58 nmol), morphine (6 nmol) and DPDPE (31 nmol) for 120, 180 and 75 min, respectively. Various doses of β-endorphin, morphine or DPDPE were then injected. The tail-flick and hot-plate tests were used as antinociceptive tests. Pretreatment of mice with β-endorphin i.c.v. reduced inhibition of the tail-flick and hot-plate responses to i.c.v. administered β-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 β-endorphin. Pretreatment of mice with DPDPE reduced inhibition of the tail-flick and hot-plate responses to DPDPE but not β-endorphin. The results indicate that one injection of β-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 β-endorphin, morphine and DPDPE produce antinociception by stimulating specific ϵ−, μ− and δ-opioid receptors, respectively.