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Potentiation of morphine antinociception by pentobarbital in female vs. male rats.
Pain. 2006 Mar; 121(1-2):115-25.PAIN

Abstract

It has been shown previously that female rats are more sensitive than males to barbiturate anesthesia, whereas males may be more sensitive than females to opioid antinociception. The aim of the present study was to determine whether enhancement of morphine antinociception by pentobarbital, previously demonstrated in male animals and humans, occurs similarly in females. Pentobarbital (50 mg/kg i.p.) produced longer-lasting anesthetic effects (loss of muscle tone, righting reflex) in gonadally intact female rats than in males, but greater antinociceptive effects in males at some time points post-injection. There were no significant sex differences in morphine-induced anesthesia or antinociception; however, 50 mg/kg pentobarbital produced greater leftward shifts in the morphine antinociceptive dose-effect curve in gonadally intact females than males, whether pentobarbital was administered 30 vs. 120 min before morphine (times at which there were no sex differences vs. sex differences, respectively, in pentobarbital's effects when administered alone). Dose-addition analysis confirmed that pentobarbital enhancement of morphine antinociception was supra-additive in both sexes; morphine also significantly enhanced pentobarbital-induced anesthesia in both sexes. In gonadectomized males, testosterone did not significantly alter pentobarbital enhancement of morphine antinociception; in contrast, in gonadectomized females, estradiol significantly attenuated the drug interaction. Estradiol did not significantly alter the effects of pentobarbital alone or morphine alone, indicating that the attenuation of the pentobarbital's potentiation of morphine antinociception in estradiol-treated rats is specific to the drug interaction. These results suggest that barbiturate potentiation of opioid antinociception may be greater in females - particularly those in low ovarian hormone states - than in males.

Authors+Show Affiliations

Craft RM
Department of Psychology, Washington State University, Pullman, WA 99164-4820, USA. craft@wsu.edu
Leitl MD
No affiliation info available

MeSH

Adjuvants, AnesthesiaAnalgesics, OpioidAnalysis of VarianceAnimalsCastrationDisease Models, AnimalDose-Response Relationship, DrugDrug SynergismEstradiolFemaleMaleMorphinePainPain MeasurementPain ThresholdPentobarbitalRatsRats, Sprague-DawleySex CharacteristicsTestosteroneTime FactorsVagina

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

16473463

Citation

Craft, Rebecca M., and Michael D. Leitl. "Potentiation of Morphine Antinociception By Pentobarbital in Female Vs. Male Rats." Pain, vol. 121, no. 1-2, 2006, pp. 115-25.
Craft RM, Leitl MD. Potentiation of morphine antinociception by pentobarbital in female vs. male rats. Pain. 2006;121(1-2):115-25.
Craft, R. M., & Leitl, M. D. (2006). Potentiation of morphine antinociception by pentobarbital in female vs. male rats. Pain, 121(1-2), 115-25.
Craft RM, Leitl MD. Potentiation of Morphine Antinociception By Pentobarbital in Female Vs. Male Rats. Pain. 2006;121(1-2):115-25. PubMed PMID: 16473463.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Potentiation of morphine antinociception by pentobarbital in female vs. male rats. AU - Craft,Rebecca M, AU - Leitl,Michael D, Y1 - 2006/02/10/ PY - 2005/09/06/received PY - 2005/11/25/revised PY - 2005/12/06/accepted PY - 2006/2/14/pubmed PY - 2006/6/3/medline PY - 2006/2/14/entrez SP - 115 EP - 25 JF - Pain JO - Pain VL - 121 IS - 1-2 N2 - It has been shown previously that female rats are more sensitive than males to barbiturate anesthesia, whereas males may be more sensitive than females to opioid antinociception. The aim of the present study was to determine whether enhancement of morphine antinociception by pentobarbital, previously demonstrated in male animals and humans, occurs similarly in females. Pentobarbital (50 mg/kg i.p.) produced longer-lasting anesthetic effects (loss of muscle tone, righting reflex) in gonadally intact female rats than in males, but greater antinociceptive effects in males at some time points post-injection. There were no significant sex differences in morphine-induced anesthesia or antinociception; however, 50 mg/kg pentobarbital produced greater leftward shifts in the morphine antinociceptive dose-effect curve in gonadally intact females than males, whether pentobarbital was administered 30 vs. 120 min before morphine (times at which there were no sex differences vs. sex differences, respectively, in pentobarbital's effects when administered alone). Dose-addition analysis confirmed that pentobarbital enhancement of morphine antinociception was supra-additive in both sexes; morphine also significantly enhanced pentobarbital-induced anesthesia in both sexes. In gonadectomized males, testosterone did not significantly alter pentobarbital enhancement of morphine antinociception; in contrast, in gonadectomized females, estradiol significantly attenuated the drug interaction. Estradiol did not significantly alter the effects of pentobarbital alone or morphine alone, indicating that the attenuation of the pentobarbital's potentiation of morphine antinociception in estradiol-treated rats is specific to the drug interaction. These results suggest that barbiturate potentiation of opioid antinociception may be greater in females - particularly those in low ovarian hormone states - than in males. SN - 0304-3959 UR - https://www.unboundmedicine.com/medline/citation/16473463/Potentiation_of_morphine_antinociception_by_pentobarbital_in_female_vs__male_rats_ DB - PRIME DP - Unbound Medicine ER -