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Hedonic sensitivity to low-dose ketamine is modulated by gonadal hormones in a sex-dependent manner

Title: Hedonic sensitivity to low-dose ketamine is modulated by gonadal hormones in a sex-dependent manner.
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Name(s): Saland, Samantha K., author
Schoepfer, Kristin J., author
Kabbaj, Mohamed, author
Type of Resource: text
Genre: Text
Date Issued: 2016-02-18
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: We recently reported a greater sensitivity of female rats to rapid antidepressant-like effects of ketamine compared to male rats, and that ovarian-derived estradiol (E2) and progesterone (P4) are essential for this response. However, to what extent testosterone may also contribute, and whether duration of response to ketamine is modulated in a sex-and hormone-dependent manner remains unclear. To explore this, we systematically investigated the influence of testosterone, estradiol and progesterone on initiation and maintenance of hedonic response to low-dose ketamine (2.5 mg/kg) in intact and gonadectomized male and female rats. Ketamine induced a sustained increase in sucrose preference of female, but not male, rats in an E2P4-dependent manner. Whereas testosterone failed to alter male treatment response, concurrent administration of P4 alone in intact males enhanced hedonic response low-dose ketamine. Treatment responsiveness in female rats only was associated with greater hippocampal BDNF levels, but not activation of key downstream signaling effectors. We provide novel evidence supporting activational roles for ovarian-, but not testicular-, derived hormones in mediating hedonic sensitivity to low-dose ketamine in female and male rats, respectively. Organizational differences may, in part, account for the persistence of sex differences following gonadectomy and selective involvement of BDNF in treatment response.
Identifier: FSU_libsubv1_wos_000370371700002 (IID), 10.1038/srep21322 (DOI)
Keywords: Anhedonia, antidepressant, brain, disorders, female rats, forced swim test, major depression, neurotrophic factor, ovariectomized rats, testosterone
Publication Note: The publisher’s version of record is available at http://www.dx.doi.org/10.1038/srep21322
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_libsubv1_wos_000370371700002
Owner Institution: FSU
Is Part Of: Scientific Reports.
2045-2322
Issue: vol. 6

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Saland, S. K., Schoepfer, K. J., & Kabbaj, M. (2016). Hedonic sensitivity to low-dose ketamine is modulated by gonadal hormones in a sex-dependent manner. Scientific Reports. Retrieved from http://purl.flvc.org/fsu/fd/FSU_libsubv1_wos_000370371700002