Loss of antinociceptive efficacy in rat pups infused with morphine from osmotic minipumps.

Abstract:

:We determined the susceptibility of two ages of rat pups to become tolerant to and dependent on morphine infusions from osmotic minipumps. Neonatal rats (postnatal day 6; P6) were infused for 72 h with morphine at 0.175 or 0.7 mg/kg/h. On P9, morphine's antinociceptive efficacy was reduced in both groups. P14 infant rats were also infused at 0.7 mg/kg/h. Unlike P9 neonates, morphine's potency was reduced in P17 infant rats, without a loss in efficacy. Yet raising the infusion rate to 1.1 mg/kg/h reduced morphine's efficacy. (3)H-DAMGO D-Ala2, N-MePhe4, Gly5-ol-enkephalin) binding revealed no change in the affinity or density of mu-opioid receptors at any age or in any treatment group. P9 and P17 pups were physically dependent on each infusion dose. Thus, chronic infusion of morphine affected both ages to such an extent that acutely administered morphine doses of even 1,000 mg/kg failed to restore antinociception. However, this effect cannot be attributed to changes in mu-opioid receptor number or affinity.

journal_name

Pharmacology

journal_title

Pharmacology

authors

Stoller DC,Thornton SR,Smith FL

doi

10.1159/000063250

subject

Has Abstract

pub_date

2002-09-01 00:00:00

pages

11-8

issue

1

eissn

0031-7012

issn

1423-0313

pii

63250

journal_volume

66

pub_type

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