Sex differences in the effects of a Kappa Opioid receptor antagonist in the forced swim test

Abigail Laman-Maharg, Alexia V. Williams, Mikaela D. Zufelt, Vanessa A. Minie, Stephanie Ramos-Maciel, Rebecca Hao, Evelyn Ordoñes Sanchez, Tiffany Copeland, Jill L Silverman, Angelina Leigh, Rodney Snyder, F. Ivy Carroll, Timothy R. Fennell, Brian C. Trainor

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

There is growing evidence that kappa opioid receptor (KOR) antagonists could be a useful class of therapeutics for treating depression and anxiety. However, the overwhelming majority of preclinical investigations examining the behavioral effects of KOR antagonists have been in male rodents. Here, we examined the effects of the long-acting KOR antagonist nor-binaltophimine (norBNI) on immobility in the forced swim test in males and females of two different rodent species (C57Bl/6J and California mice). Consistent with previous reports, norBNI (10 mg/kg) decreased immobility in the forced swim test for male C57Bl/6J and California mice. Surprisingly, dose-response studies in female C57Bl/6J and California mice showed that norBNI did not reduce immobility. Pharmacokinetic analyses showed that metabolism and brain concentrations of norBNI were similar in male and female C57Bl/6J. In the nucleus accumbens of male but not female C57Bl/6J, norBNI increased phosphorylation of c-Jun N-terminal kinase (pJNK), a putative mechanism for norBNI action. However, no differences in pJNK were observed in male or female California mice. Together, these results suggest that immobility in the forced swim test is less dependent on endogenous KOR signaling in female rodents and highlight the importance of examining the effects of possible therapeutic agents in both males and females.

Original languageEnglish (US)
Article number93
JournalFrontiers in Pharmacology
Volume9
Issue numberFEB
DOIs
StatePublished - Feb 14 2018

Fingerprint

kappa Opioid Receptor
Narcotic Antagonists
Sex Characteristics
Rodentia
JNK Mitogen-Activated Protein Kinases
Phosphorylation
Nucleus Accumbens
Therapeutic Uses
Anxiety
Pharmacokinetics
Depression
Brain

Keywords

  • Antidepressants
  • Kappa opioid receptors
  • Nucleus accumbens
  • Sex differences
  • Stress

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Laman-Maharg, A., Williams, A. V., Zufelt, M. D., Minie, V. A., Ramos-Maciel, S., Hao, R., ... Trainor, B. C. (2018). Sex differences in the effects of a Kappa Opioid receptor antagonist in the forced swim test. Frontiers in Pharmacology, 9(FEB), [93]. https://doi.org/10.3389/fphar.2018.00093

Sex differences in the effects of a Kappa Opioid receptor antagonist in the forced swim test. / Laman-Maharg, Abigail; Williams, Alexia V.; Zufelt, Mikaela D.; Minie, Vanessa A.; Ramos-Maciel, Stephanie; Hao, Rebecca; Sanchez, Evelyn Ordoñes; Copeland, Tiffany; Silverman, Jill L; Leigh, Angelina; Snyder, Rodney; Ivy Carroll, F.; Fennell, Timothy R.; Trainor, Brian C.

In: Frontiers in Pharmacology, Vol. 9, No. FEB, 93, 14.02.2018.

Research output: Contribution to journalArticle

Laman-Maharg, A, Williams, AV, Zufelt, MD, Minie, VA, Ramos-Maciel, S, Hao, R, Sanchez, EO, Copeland, T, Silverman, JL, Leigh, A, Snyder, R, Ivy Carroll, F, Fennell, TR & Trainor, BC 2018, 'Sex differences in the effects of a Kappa Opioid receptor antagonist in the forced swim test', Frontiers in Pharmacology, vol. 9, no. FEB, 93. https://doi.org/10.3389/fphar.2018.00093
Laman-Maharg A, Williams AV, Zufelt MD, Minie VA, Ramos-Maciel S, Hao R et al. Sex differences in the effects of a Kappa Opioid receptor antagonist in the forced swim test. Frontiers in Pharmacology. 2018 Feb 14;9(FEB). 93. https://doi.org/10.3389/fphar.2018.00093
Laman-Maharg, Abigail ; Williams, Alexia V. ; Zufelt, Mikaela D. ; Minie, Vanessa A. ; Ramos-Maciel, Stephanie ; Hao, Rebecca ; Sanchez, Evelyn Ordoñes ; Copeland, Tiffany ; Silverman, Jill L ; Leigh, Angelina ; Snyder, Rodney ; Ivy Carroll, F. ; Fennell, Timothy R. ; Trainor, Brian C. / Sex differences in the effects of a Kappa Opioid receptor antagonist in the forced swim test. In: Frontiers in Pharmacology. 2018 ; Vol. 9, No. FEB.
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