Effects of gonadectomy and hormone replacement on a spontaneous novel object recognition task in adult male rats
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.
References (72)
Gonadectomy in adult life increases tyrosine hydroxylase immunoreactivity in the prefrontal cortex and decreases open field activity in male rats
Neuroscience
(1999)Extensive cytotoxic lesions involving both the rhinal cortices and area TE impair recognition but spare spatial alternation in the rat
Brain Res. Bull.
(1997)Correlation between testosterone, gonadotropins and prolactin and severity of negative symptoms in male patients with chronic schizophrenia
Schizophr. Res.
(2006)Sex differences in open-field behavior in the rat: the inductive and activational role of gonadal hormones
Physiol. Behav.
(1975)Effects of gonadal hormones and persistent pain on non-spatial working memory in male and female rats
Behav. Brain Res.
(2001)- et al.
Extending the spontaneous preference test of recognition: evidence of object-location and object-context recognition
Behav. Brain Res.
(1999) - et al.
Androgens' effects to enhance learning may be mediated in part through actions at estrogen receptor-beta in the hippocampus
Neurobiol. Learn. Mem.
(2007) - et al.
A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data
Behav. Brain Res.
(1988) Neurotoxic lesions of the perirhinal cortex do not mimic the behavioural effects of fornix transection in the rat
Behav Brain Res.
(1996)5alpha-reduced androgens may have actions in the hippocampus to enhance cognitive performance of male rats
Psychoneuroendocrinology.
(2004)