Naloxone prevention of morphine LDR curve flattening associated with high-dose tolerance
✍ Scribed by R. F. Mucha; H. Kalant
- Book ID
- 104771678
- Publisher
- Springer
- Year
- 1981
- Tongue
- English
- Weight
- 220 KB
- Volume
- 75
- Category
- Article
- ISSN
- 0033-3158
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✦ Synopsis
Male wistar rats, previously made tolerant to morphine by at least 3 weeks of daily intraperitoneal (IP) injections of 20 mg/kg morphine-SO4 (MS), were then given 9 200 mg/kg MS daily for 4 or 5 days. Tail immersion tests of antinociception, carried out before and after the 200 mg/kg MS treatment, indicated that the additional morphine treatment was followed by a large further decrease in opiate sensitivity, characterized by decreased slope of the logdose/response curve (LDR curve flattening). The further decrease in opiate sensitivity was substantially reduced by naloxone-HC1 (IP) in a dose of 10 mg/kg given 30 min before and 8 h after the 200 mg/kg MS injections, or a dose of 4 mg/kg given 45 rain after the MS. It was concluded that LDR curve flattening produced by high doses of MS is mediated by specific opiate receptors, and is a true expression of a high degree of opiate tolerance in the intact rat.