Δ-opioid Receptor Antagonist Naltrindole Research Articles

Hypothalamic Effects of C‐Type Natriuretic Peptide on Luteinizing Hormone Secretion

Previous studies have demonstrated hypothalamic sites of action of A-type natriuretic peptide (ANP) in the inhibition of luteinizing hormone (LH) secretion, acting at least in part, via an opiatergic mechanism. C-type natriuretic peptide (CNP) was identified recently and is thought to be the predominant brain form of the family of natriuretic peptides. Third cerebroventricular injection of CNP in doses of either 0.1, 1.0 or 2.0 nmole significantly inhibited, in a dose-related fashion, plasma LH levels when compared to levels present in saline-injected controls. When compared to the LH-inhibiting action of ANP, CNP appeared more potent (effective at lower doses) and efficacious (longer duration of action for the maximum effective doses). The LH-inhibiting effect of CNP was blocked by prior treatment with the δ-opioid receptor antagonist naltrindole (50 μg), suggesting an enkephalinergic mechanism of action. CNP in log doses ranging from 0.01 to 1,000 nM did not significantly alter LH release from dispersed pituitary cells harvested from random cycle female rats, either under static or dynamic (perifusion) incubation conditions. These results indicate that CNP, like ANP, acts at the hypothalamic level to alter LH secretion and suggest that CNP may be the preferential neuroactive members of this family of peptides.

Antinociception after intracerebroventricular administration of naltrindole in the mouse

Intracerebroventricular (i.c.v.) injection of the δ-opioid receptor antagonist naltrindole hydrochloride (2.2–22.2 nmol) in mice produced a dose-dependent increase in tail flick and hot plate latencies with respective ED 50 and 95% confidence limits of 10.6 (8.3–13.9) and 16.4 (9.2–62.3) nmol. This increase in response latencies was antagonized by 1 mg/kg s.c. naloxone or by i.c.v. coadministration of 1.4 nmol ICI-174,864, a selective peptidergic δ-receptor antagonist. Pretreatment 24 h earlier with the irreversible μ-receptor antagonist β-funaltrexamine (6 nmol i.c.v.) or 1 h earlier with the selective κ-receptor antagonist nor-binaltorphimine (100 nmol i.c.v.) did not attenuate the antinociceptive effects of naltrindole. These data indicate that high doses of naltrindole may have agonist activity at supraspinal δ-opioid receptors in the mouse.

Effects of the δ-opioid receptor antagonist naltrindole on opioid induced in vivo release of corticosterone

Effects of the δ-opioid receptor antagonist naltrindole on opioid induced in vivo release of corticosterone

Further Evidence for the Implication of a κ-Opioid Receptor Mechanism in the Production of Psychological Stress-Induced Analgesia

The analgesic effect induced by exposure to psychological stress, using a communication box (psychological stress-induced analgesia, PSY-SIA), was completely antagonized by 10 min pretreatment with 0.5,1 and 2 mg/kg of nor-binaltorphimine and with 0.5 and 1 mg/kg of Mr2266, selective κ-opioid receptor antagonists, in the tail pinch method. Neither footshock (FS)-nor forced swimming (SW)-SIA was affected by these antagonists. The selective δ-opioid receptor antagonist naltrindole, at doses up to 20 mg/kg, had no appreciable effect on PSY-SIA. Daily morphine treatment, 10 mg/kg, s.c., resulted in tolerance to the analgesic effect, and concurrent exposure to PSY-stress suppressed the development of morphine tolerance. The substitution of treatment with U-50,488H for PSY-stress still resulted in analgesia on the initial day; and likewise, the suppression by U-50,488H of the development of morphine tolerance was replicated by PSY-stress. Pretreatment with nor-binaltorphimine antagonized the suppressive effect of PSY-stress on the development of morphine tolerance without affecting the analgesic effect of morphine per se. These results provide further evidence that PSY-SIA involves the mediation by κ-opioid receptor mechanisms.