No relation of plasma morphine level to the severity of naloxone-induced withdrawal in acute morphine-dependent rats.
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.
Kishioka
S
S
Department of Pharmacology, Wakayama Medical College, Japan.
Inoue
N
N
Nishida
S
S
Fukunaga
Y
Y
Yamamoto
H
H
D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D008297:Male; D009020:Morphine / Q000097:blood* / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome; D013997:Time Factors
D009270:Naloxone; D009020:Morphine; D003345:Corticosterone