No relation of plasma morphine level to the severity of naloxone-induced withdrawal in acute morphine-dependent rats

Jpn J Pharmacol. 1995 Nov;69(3):187-93. doi: 10.1254/jjp.69.187.

Abstract

Plasma morphine concentration and naloxone-precipitated withdrawal body weight loss and plasma corticosterone (PCS) increase were determined at 12, 18 and 24 hr after i.v. infusion of morphine at a constant rate of 10 mg/kg/hr for 4 hr in Sprague-Dawley rats. Plasma morphine concentration declined 98.0% within 12 hr and further declined 58.8% during 12-24 hr after morphine infusion. There was a significant difference between plasma morphine concentrations at 12 and 24 hr after the morphine infusion. Naloxone (0.5 and 2.0 mg/kg)-precipitated withdrawal, but not spontaneous withdrawal, was elicited at 12-24 hr after the morphine infusion, and the severity of withdrawal precipitated by 2.0 mg/kg naloxone was the same at 12-24 hr after the morphine infusion. Furthermore, there was no significant correlation between plasma morphine concentration and body weight loss or PCS increase. The results suggest that a constant degree of morphine dependence is sustained during 12-24 hr after the morphine infusion and the severity of naloxone-precipitated withdrawal is not related to the plasma morphine concentration at the time of naloxone injection, that is, the rate of morphine removal from its receptor sites.

MeSH terms

  • Animals
  • Body Weight / drug effects*
  • Corticosterone / blood
  • Dose-Response Relationship, Drug
  • Male
  • Morphine / blood*
  • Morphine / pharmacology
  • Naloxone / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Substance Withdrawal Syndrome*
  • Time Factors

Substances

  • Naloxone
  • Morphine
  • Corticosterone