title: Continuous infusion versus intermittent bolus dosing of morphine: a comparison of analgesia, tolerance, and subsequent voluntary morphine intake.
abstract: Improved utilization of continuous or intermittent opioid administration in pain treatment necessitates a comparison of the antinociceptive effect and tolerance of these two treatment methods. More importantly, the effect of treatment method on subsequent opioid consumption has not been directly compared, although it is widely assumed that continuous opioid treatment may produce lower addictive liability relative to intermittent opioid treatment. In this study, we compared the antinociceptive effect and tolerance of morphine in rats that received repeated injection (10 mg/kg twice daily for 7 days) or continuous infusion (20 mg/kg daily for 7 days) subcutaneously and the self-administration of intravenous morphine in these rats after 7 days of withdrawal. Both intermittent and continuous morphine treatment produced antinociceptive tolerance, but the exhibition of tolerance differed. Moreover, intermittent morphine pretreatment facilitated subsequent morphine self-administration, whereas continuous morphine pretreatment produced minimal effects, as shown by comparable levels of active responses and morphine consumption between continuous morphine and saline-treated rats. These results suggest that the administration method of opioid should be selected according to the specific pain situation and that continuous opioid administration or long-acting therapy may be advantageous, producing less influence on drug-taking behavior than intermittent administration of short-acting drugs.
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, People's Republic of China. Electronic address: yg1st@163.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Yu
authors.affiliation: Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, 42 Xibei Street, Ningbo 315010, People's Republic of China.
authors.forename: Fu-Qiang
authors.initials: FQ
authors.lastname: Zhang
authors.affiliation: Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, 42 Xibei Street, Ningbo 315010, People's Republic of China.
authors.forename: Shuai-En
authors.initials: SE
authors.lastname: Tang
authors.affiliation: Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, 42 Xibei Street, Ningbo 315010, People's Republic of China.
authors.forename: Miao-Jun
authors.initials: MJ
authors.lastname: Lai
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, People's Republic of China. Electronic address: ruibinsu@126.com.
authors.forename: Rui-Bin
authors.initials: RB
authors.lastname: Su
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, People's Republic of China.
authors.forename: Ze-Hui
authors.initials: ZH
authors.lastname: Gong
mesh_terms: D061605:Administration, Intravenous; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D016503:Drug Delivery Systems; D004361:Drug Tolerance; D006358:Hot Temperature / Q000009:adverse effects; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine
keywords: Antinociception; Continuous infusion; Intermittent injection; Morphine; Self-administration