Loss of antinociceptive efficacy in rat pups infused with morphine from osmotic minipumps.
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.
Stoller
Dawn C
DC
Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, Va 23298-0613, USA.
Thornton
Suzanne R
SR
Smith
Forrest L
FL
D000367:Age Factors; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D066298:In Vitro Techniques; D007260:Infusion Pumps; D009020:Morphine / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D009021:Morphine Dependence / Q000209:etiology; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000209:etiology
D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D009020:Morphine