Elsevier

Hormones and Behavior

Volume 54, Issue 2, July 2008, Pages 244-252
Hormones and Behavior

Effects of gonadectomy and hormone replacement on a spontaneous novel object recognition task in adult male rats

https://doi.org/10.1016/j.yhbeh.2008.04.001Get rights and content

Abstract

Recent studies in adult male rats have shown that gonadal hormones influence performance on certain working memory and other types of cognitive tasks that are sensitive to lesions of the medial and/or orbital prefrontal cortices. This study asked whether gonadal hormone modulation of prefrontal cortical function in males also extends to the perirhinal division of the rat prefrontal cortex. Specifically, sham-operated control, gonadectomized, and gonadectomized rats supplemented with testosterone propionate or estradiol were tested on a spontaneous novel object recognition task, a paradigm where performance has been shown to be impaired by perirhinal cortical lesions. Using analyses of variance, regression analyses and post-hoc testing to evaluate group differences, it was found that during both the sample and test trials of the task all four groups spent similar absolute and proportional amounts of time ambulating, rearing, stationary, and exploring the two objects present. All groups also explored each of the two identical objects present during sample trials equally. However, during the test trials, only the control and gonadectomized rats given testosterone showed the expected increase in exploration of the novel objects presented, whereas the gonadectomized and gonadectomized, estradiol-supplemental groups continued to explore the novel and familiar objects equally. That regression analyses also identified significant correlations between low bulbospongiosus muscle weight and impaired novel vs. familiar object discrimination further indicates that gonadectomy in adult male rats adversely affects spontaneous novel object recognition in an androgen-sensitive, estrogen-insensitive manner.

Introduction

Although there may be a longer history of study regarding gonadal hormone influence over the cognitive, mnemonic and executive functions of the prefrontal cortices in females (Berman, 1997, Gibbs and Gabor, 2003, Keenan, 2001, Korol, 2004), there is growing evidence that gonadal steroids also impact prefrontal cortical operations in males. For example, in both young and aged men, circulating testosterone levels have been positively correlated with performance in prefrontal tasks including mental rotation, verbal recall and divided attention (Cherrier, 2002, Cherrier, 2001, Christiansen and Knussmann, 1987, Moffat and Hampson, 1996, Yaffe, 2002). Studies in animal models also suggest an importance of gonadal steroid stimulation for prefrontal cortical function in males. For example, gonadectomy in adult male rats has been shown to significantly impair performance in maze and operant tests of spatial (Daniel, 2003, Kritzer, 2007, Kritzer, 2001) and non-spatial (Ceccarelli et al., 2001) working memory and behavioral flexibility (Kritzer et al., 2007), which are processes that are dependent on the medial prefrontal cortices (Dias and Aggleton, 2000, Kesner, 1996, Lacroix, 2002, Schwabe, 2004, Taylor, 2003), as well as performance on a progressive reward ratio task (Kritzer et al., 2007) which is sensitive to lesions of the orbital prefrontal cortices (Kheramin et al., 2005). In this study, analyses of hormone sensitivity were extended to a task sensitive in part to lesions of the perirhinal prefrontal cortices, a spontaneous novel object recognition (NOR) task, to test the hypothesis that functions mediated by this third major division of the prefrontal cortex may also be sensitive to long-term gonadectomy and hormone replacement in adult male subjects. The novel object recognition task is in part a working memory paradigm that is sensitive to both hippocampal (Gaskin, 2003, Gould, 2002, Gulinello, 2006) and cortical lesions placed in and around the prefrontal areas surrounding the rhinal fissure (Aggleton, 1997, Barker, 2007, Buffalo, 2006, Cowell, 2006, Ennaceur, 1996, Ennaceur, 1997, Moses, 2005, Mumby and Pinel, 1994, Winters, 2004). It is also a task where hormone sensitivity has been previously established in findings of sex and/or estrous cycle differences in NOR performance (Bisagno, 2003, Ghi, 1999, Sutcliffe, 2007, Walf, 2006), and in the attenuation of NOR deficits in ovariectomized female rats (with and without chronic stress) by giving ovariectomized animals estradiol (Luine, 2006, Luine, 2003, Wallace, 2006). Here, NOR performance was assessed for the first time in gonadectomized and hormone-replaced adult male rats. In view of previous evidence for effects of gonadectomy on open-field behavior (Adler, 1999, Kerr, 1996, Slob, 1986) quantitative assessments of all major behaviors exhibited by the animals including ambulation and rearing were also made alongside those of object exploration to determine whether and to what extent hormone effects on these ancillary behaviors might affect outcome measures of novel object recognition and/or discrimination in males.

Section snippets

Animal subjects

Thirty-one adult male Sprague–Dawley rats (Taconic Farms, Germantown, NY) were used. Rats weighed 200–250 g at time of surgery and 275–400 g when testing began. Animals were divided into four treatment groups: sham-operated controls (n = 8, CTRL), rats that were gonadectomized (n = 8, GDX), and gonadectomized rats that were supplemented with testosterone propionate (n = 7, GDX-TP), or 17-β-estradiol (n = 8, GDX-E). Throughout, subjects were housed under a 12/12 light/dark cycle with food and water

Effectiveness of hormone treatment

Bulbospongiosus muscle (BSM) weights showed expected group differences. Thus, the CTRL and GDX-TP animals had average BSM weights of 1.22 and 1.17 g, respectively, whereas GDX and GDX-E animals had average BSM weights of 0.30 and 0.27 g, respectively. An ANOVA that compared weights across treatment groups revealed significant main effects of hormone treatment [F(3,27) = 59.01, p < 0.0001], and post-hoc tests confirmed that the androgen-sensitive BSM weights of the control and GDX-TP groups did not

Discussion

 Recent studies in adult male rats have identified modulatory roles for gonadal steroids on working memory and other types of cognitive tasks that are known to be sensitive to lesions of the medial (Ceccarelli, 2001, Daniel, 2003, Kritzer, 2007, Turvin, 2007) and orbital (Kheramin, 2003, Kritzer, 2007) divisions of the prefrontal cortices in rats. The studies presented here now demonstrate gonadal hormone sensitivity for a spontaneous NOR task that is sensitive in part to lesions of the third

Acknowledgments

The authors thank Dr. Victoria Luine for her encouragement in using the NOR and her assistance in the initial design of the experiments.

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