Possible Involvement of the Total Amount of Morphine Infused in the Development of Acute Morphine Dependence in Rats

The Japanese Journal of Pharmacology

Norihiro Inoue¹  Shigeru Nishida¹  Yuko Fukunaga¹  Shiroh Kishioka¹  Hiroyuki Yamamoto¹ 

[1] Department of Pharmacology, Wakayama Medical College

关键词: Intravenous morphine infusion;    Naloxone-precipitated withdrawal;    Total amount of morphine infused;    Plasma morphine concentration;    Duration of morphine infusion;   

DOI  :  10.1254/jjp.70.17

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(20)Cited-By(3)The severity of naloxone-precipitated withdrawal in rats infused intravenously with morphine at the rates of 2.5, 5 and 10 mg/kg/hr over various time periods was investigated. Plasma morphine concentration reached a constant and rate-dependent level at 1 hr after the start of morphine infusion, and this level was maintained until the termination of infusion. Naloxone (2.0 mg/kg, s.c.) was challenged 18 hr after infusion was stopped, and the withdrawal was evaluated by plasma corticosterone (PCS) increase, diarrhea and body weight loss. The incidence of naloxone-precipitated withdrawal signs was related to both the infusion rate and duration of morphine infusion. The duration of morphine infusion (ET50) needed to elicit naloxone-precipitated PCS increase and diarrhea in 50% of the rats was inversely related to the morphine infusion rates, but the total amount of infused morphine (EA50) that elicited naloxone-precipitated withdrawals in 50% of rats was the same at all infusion rates. These results suggest that the total amount of morphine infused may play an important role in the development of acute physical dependence on morphine rendered by continuous intravenous morphine infusion for 1-8 hr.

【 授权许可】

Unknown