Journal article
Sex Differences in Discriminative Stimulus and Diuretic Effects of the κ Opioid Agonist U69,593 in the Rat
Pharmacology, biochemistry and behavior, Vol.61(4), pp.395-403
1998
Handle:
https://hdl.handle.net/2376/115839
PMID: 9802834
Abstract
Female and male rats were trained to discriminate the κ opioid agonist (5α,7α,8β)-(−)-
N-methyl-[7-(1-pyrrolidinyl)-1-oxaspiro(4,5)dec-8-yl]benzeneacetamide (U69,593, 0.13 mg/kg SC) from vehicle using a FR-10 schedule of food reinforcement. Female rats took significantly longer than males to acquire the discrimination (66.9 vs. 44.1 sessions, respectively), and the ED
50 for U69,593 discrimination was significantly higher in females than in males (0.074 vs. 0.025 mg/kg). The time course of U69,593 discrimination also differed between the sexes: peak and offset occurred earlier in females than in males. The ED
50 for bremazocine substitution was significantly higher in females than in males (0.0039 vs. 0.0006 mg/kg), whereas ethylketazocine substituted for U69,593 in all males and five of seven females, with no sex difference in substitution ED
50. Morphine and BW373U86 did not substitute for U69,593 in a majority of rats of either sex. U69,593 also produced significantly less urine output/dose in females compared to males (e.g., 5.92 vs. 14.83 ml urine/kg body weight after 1.0 mg/kg U69,593), but was equipotent between the sexes in producing hot-plate antinociception. There was no sex difference in response rate-decreasing effect of any opioid agonist tested, and no sex difference in brain/blood ratio of [
3H]U69,593 measured in a separate group of rats, suggesting that sex differences observed in some effects of U69,593 probably are not due to sex differences in U69,593 pharmacokinetics. When retested at the end of the study, U69,593 and bremazocine were no longer differentially potent as discriminative stimuli in females and males, suggesting that factors that change over time (e.g., additional training, age, hormonal status) may contribute to initial sex differences in discriminability of U69,593.
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Details
- Title
- Sex Differences in Discriminative Stimulus and Diuretic Effects of the κ Opioid Agonist U69,593 in the Rat
- Creators
- Rebecca M Craft - Department of Psychology, Pharmacology and Physiology, Washington State University, Pullman, WA 99164-4820 USAPaul J Kruzich - Department of Psychology, Pharmacology and Physiology, Washington State University, Pullman, WA 99164-4820 USAJill S Boyer - Department of Psychology, Pharmacology and Physiology, Washington State University, Pullman, WA 99164-4820 USAJoseph W Harding - Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, WA 99164-4820 USAJody M Hanesworth - Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, WA 99164-4820 USA
- Publication Details
- Pharmacology, biochemistry and behavior, Vol.61(4), pp.395-403
- Academic Unit
- Psychology, Department of; Integrative Physiology and Neuroscience, Department of
- Publisher
- Elsevier Inc
- Identifiers
- 99900547896301842
- Language
- English
- Resource Type
- Journal article