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Influence of low doses of naltrexone on morphine antinociception and morphine tolerance in male and female rats of four strains.
Pain 2006; 122(1-2):90-101PAIN

Abstract

In a recently proposed bimodal opioid receptor model, the inhibitory actions of opioids on action potential duration in dorsal root ganglion neurons have been proposed to produce antinociception, and the excitatory actions of hyperalgesia. Recent studies indicate that selectively blocking these excitatory actions with low doses of opioid antagonists enhances opioid antinociception and attenuates the development of opioid tolerance. To determine if the excitatory actions of opioids contribute to sex as well as strain differences in opioid sensitivity, the effects of morphine alone and in combination with low doses of naltrexone were examined in male and female rats of four strains. The strains examined differed in their sensitivity to opioid antinociception and magnitude of sex differences in opioid sensitivity. All testing was conducted using a thermal tail-flick procedure with the nociceptive stimulus intensity adjusted so that baseline latencies were comparable across strains/sexes. In chronic studies, the morphine dosing regimen was adjusted in each strain/sex to produce comparable levels of tolerance. In each of the strains tested, morphine produced dose-dependent increases in antinociception, with differences in morphine potency observed across strains and sexes. In male and female Sprague-Dawley and Long-Evans rats, naltrexone enhanced morphine antinociception and attenuated the development of morphine tolerance. These effects were not observed in F344 and Lewis rats, even when tests were conducted across a range of morphine and naltrexone doses. These results suggest that the ability of low doses of naltrexone to enhance opioid antinociception does not contribute to sex or rat strain differences in opioid sensitivity.

Authors+Show Affiliations

Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3270, USA. jterner@yoda.bsd.uchicago.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16527399

Citation

Terner, Jolan M., et al. "Influence of Low Doses of Naltrexone On Morphine Antinociception and Morphine Tolerance in Male and Female Rats of Four Strains." Pain, vol. 122, no. 1-2, 2006, pp. 90-101.
Terner JM, Barrett AC, Lomas LM, et al. Influence of low doses of naltrexone on morphine antinociception and morphine tolerance in male and female rats of four strains. Pain. 2006;122(1-2):90-101.
Terner, J. M., Barrett, A. C., Lomas, L. M., Negus, S. S., & Picker, M. J. (2006). Influence of low doses of naltrexone on morphine antinociception and morphine tolerance in male and female rats of four strains. Pain, 122(1-2), pp. 90-101.
Terner JM, et al. Influence of Low Doses of Naltrexone On Morphine Antinociception and Morphine Tolerance in Male and Female Rats of Four Strains. Pain. 2006;122(1-2):90-101. PubMed PMID: 16527399.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Influence of low doses of naltrexone on morphine antinociception and morphine tolerance in male and female rats of four strains. AU - Terner,Jolan M, AU - Barrett,Andrew C, AU - Lomas,Lisa M, AU - Negus,S Stevens, AU - Picker,Mitchell J, Y1 - 2006/03/09/ PY - 2005/05/04/received PY - 2005/12/13/revised PY - 2006/01/17/accepted PY - 2006/3/11/pubmed PY - 2006/6/7/medline PY - 2006/3/11/entrez SP - 90 EP - 101 JF - Pain JO - Pain VL - 122 IS - 1-2 N2 - In a recently proposed bimodal opioid receptor model, the inhibitory actions of opioids on action potential duration in dorsal root ganglion neurons have been proposed to produce antinociception, and the excitatory actions of hyperalgesia. Recent studies indicate that selectively blocking these excitatory actions with low doses of opioid antagonists enhances opioid antinociception and attenuates the development of opioid tolerance. To determine if the excitatory actions of opioids contribute to sex as well as strain differences in opioid sensitivity, the effects of morphine alone and in combination with low doses of naltrexone were examined in male and female rats of four strains. The strains examined differed in their sensitivity to opioid antinociception and magnitude of sex differences in opioid sensitivity. All testing was conducted using a thermal tail-flick procedure with the nociceptive stimulus intensity adjusted so that baseline latencies were comparable across strains/sexes. In chronic studies, the morphine dosing regimen was adjusted in each strain/sex to produce comparable levels of tolerance. In each of the strains tested, morphine produced dose-dependent increases in antinociception, with differences in morphine potency observed across strains and sexes. In male and female Sprague-Dawley and Long-Evans rats, naltrexone enhanced morphine antinociception and attenuated the development of morphine tolerance. These effects were not observed in F344 and Lewis rats, even when tests were conducted across a range of morphine and naltrexone doses. These results suggest that the ability of low doses of naltrexone to enhance opioid antinociception does not contribute to sex or rat strain differences in opioid sensitivity. SN - 1872-6623 UR - https://www.unboundmedicine.com/medline/citation/16527399/Influence_of_low_doses_of_naltrexone_on_morphine_antinociception_and_morphine_tolerance_in_male_and_female_rats_of_four_strains_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3959(06)00047-9 DB - PRIME DP - Unbound Medicine ER -