Antinociception versus serum concentration relationships following acute administration of intravenous morphine in male and female Sprague-dawley rats: Differences between the tail flick and hot plate nociceptive tests

South, Samantha M., Edwards, Stephen R. and Smith, Maree T. (2009) Antinociception versus serum concentration relationships following acute administration of intravenous morphine in male and female Sprague-dawley rats: Differences between the tail flick and hot plate nociceptive tests. Clinical and Experimental Pharmacology and Physiology, 36 1: 20-28. doi:10.1111/j.1440-1681.2008.05019.x


Author South, Samantha M.
Edwards, Stephen R.
Smith, Maree T.
Title Antinociception versus serum concentration relationships following acute administration of intravenous morphine in male and female Sprague-dawley rats: Differences between the tail flick and hot plate nociceptive tests
Journal name Clinical and Experimental Pharmacology and Physiology   Check publisher's open access policy
ISSN 0305-1870
1440-1681
Publication date 2009-01-01
Year available 2008
Sub-type Article (original research)
DOI 10.1111/j.1440-1681.2008.05019.x
Open Access Status
Volume 36
Issue 1
Start page 20
End page 28
Total pages 9
Place of publication Richmond, Vic., Australia
Publisher Wiley-Blackwell Publishing Asia
Language eng
Subject C1
920111 Nervous System and Disorders
111501 Basic Pharmacology
111504 Pharmaceutical Sciences
Abstract Antinociception versus serum morphine concentration relationships were defined in male and female Sprague-Dawley rats administered single intravenous (i.v.) bolus doses of morphine, using the hot plate (2.1-14 mg/kg) and tail flick tests (1-8 mg/kg).
Formatted abstract
1. Antinociception versus serum morphine concentration relationships were defined in male and female Sprague-Dawley rats administered single intravenous (i.v.) bolus doses of morphine, using the hot plate (2.1–14 mg/kg) and tail flick tests (1–8 mg/kg).

2. Serum concentrations of morphine and morphine-3-glucuronide (M3G), its major metabolite in the rat, were assayed using high-performance liquid chromatography (HPLC) with electrochemical detection.

3. Significantly higher (P < 0.05) values of peak antinociception (approximately 1.7-fold), as well as the extent and duration of antinociception (approximately fourfold), were observed in male compared with female rats administered 10 mg/kg morphine in the hot plate test. Although there were no significant sex-related differences in the area under the serum morphine concentration versus time curve (AUC) at this dose, systemic exposure to M3G (M3G AUC) was significantly higher (approximately twofold; P < 0.05) in female than male rats.

4. In contrast with most previous studies investigating sex differences in morphine antinociception in rats, the antinociceptive effects of single i.v. doses of morphine (1–8 mg/kg) in the tail flick test did not differ significantly between male and female rats.

5. Morphine ED50 and EC50 values (95% confidence intervals) for antinociception in the hot plate test were significantly lower (P < 0.05) in male rats (ED50 8.4 mg/kg (7.6–9.2); EC50 1.8 nmol/L (1.5–2.1)) compared with female rats (ED50 10.6 mg/kg (9.1–12.0); EC50 3.7 nmol/L (3.4–4.1)). However, in the tail flick test, there was no significant difference between male and female rats in ED50 (1.8 (0.4–3.3) and 1.4 mg/kg (0.4–2.5), respectively) or EC50 (0.5 (0.3–0.6) and 0.4 nmol/L (0.2–0.5), respectively) values.

6. Supraspinal attenuation of morphine antinociception by M3G may account for these differences.
Keyword Antinociception
Hot plate
Morphine-3-glucuronide
Morphine
Rat
Serum concentration
Sex differences
Tail flick
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article first published online: 30 JUL 2008

 
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Created: Thu, 16 Apr 2009, 00:06:52 EST by Elizabeth Pyke on behalf of Faculty Of Health Sciences