Assessment of the effects of sex and sex hormones on spatial cognition in adult rats using the Barnes maze

Abstract

Although sex differences and hormone effects on spatial cognition are observed in humans and animals, consensus has not been reached regarding exact impact on spatial working or reference memory. Recent studies in rats suggest that stress and/or reward, which are often different in tasks used to assess spatial cognition, can contribute to the inconsistencies in the literature. To minimize the impact of these sex- and sex hormone-sensitive factors, we used the Barnes maze to compare spatial working memory, spatial reference memory and spatial learning strategy in adult male, female, gonadectomized (GDX) male, and GDX male rats supplemented with 17β-estradiol (E) or testosterone propionate (TP). Rats received four acquisition trials, four trials 24 h later, and a single retention trial one week after. Males and females acquired the task during the first four trials and retained the task thereafter. In contrast, GDX rats took longer to acquire the task and showed retention deficits at 1 week. All deficits were attenuated similarly by TP and E. Assessment of search patterns also showed that strategies in the males transitioned from random to spatially focused and eventually direct approaches to the goal. However, this transition was faster in control and GDX-TP than in GDX and GDX-E rats. In contrast, the females almost invariantly followed the maze edge in thigmotactic, serial searches. Thus, while Barnes maze reveals activational, in part estrogenic effects on spatial cognition in males, its amenability to animals' use of multiple strategies may limit its ability to resolve mnemonic differences across sex.

Characterization of exploratory activity and learning ability of healthy and “schizophrenia-like” rats in a square corridor system (AMBITUS)

“…Regarding the differences between male and female rats, the female rats had enhanced exploratory activity, but no differences in cognitive functions were observed. In most tests of allocentric navigation in rodents, male animals show an advantage compared with female animals, while in some egocentric navigation tasks, female rats performed better than male rats (Vorhees & Williams, 2014), or no sex differences were observed; thus, the sex differences depend on the specific task parameters and/or configurations Roof & Stein, 2001;Vorhees & Williams, 2014;Sutcliffe, Marshall, & Neill, 2007;Locklear & Kritzer, 2014). The new substrain of rats developed in our laboratory showed decreased exploratory activity and learning ability in the AMBITUS system, which is in agreement with the results obtained recently in novel object recognition and the hole-board tests (Petrovszki et al, 2013;Kekesi et al, 2015), and it suggests that this system can be applied to reveal the abnormalities in these parameters of rats with different impairments.…”

“…Several methods are available to determine the learning ability of rodents during relatively short time period and/or repeated short trials, including novel object recognition, hole-board, and several mazes, e.g., Y maze, T maze, Morris Water maze, Barnes maze, or radial mazes with different number of arms (Casarrubea, Sorbera, Magnusson, & Crescimanno, 2010;Xu et al, 2013;Chambon, Wegener, Gravius, & Danysz, 2011;Petrovszki et al, 2013;Fitzgerald et al, 1985;Chrobal et al, 1987;Gordan et al, 2012;Locklear & Kritzer, 2014;McLean, Woolley, & Neill, 2009;van der Staay, Gieling, Pinzón, Nordquist, & Ohl, 2012;Vorhees & Williams, 2014;Roof & Stein, 2001;Vorhees & Williams, 2014). Other, more sophisticated methods, such as tasks with touch screen or lever press, require very intensive and long-lasting learning sessions (Brown et al, 2012;Chen, Wong, Chapman, & Pemberton, 2009;de Bruin et al, 2013;Dunnett, Fuller, Rosser, & Brooks, 2012;Nemeth et al, 2002;Preissmann et al, 2011;Sabbagh, Heaney, Bolton, Murtishaw, & Kinney, 2012;Bussey et al, 2008;George, RodriguezSantiago, Riley, & Abelson, 2015).…”

Sex steroid hormones matter for learning and memory: estrogenic regulation of hippocampal function in male and female rodents

“…However, chronic systemic administration of either E 2 or testosterone reversed gonadectomy-induced impairments in a different spatial memory task, the Barnes maze (Locklear and Kritzer 2014). The discrepant effects of testosterone in these spatial tasks may result from differential sensitivity of spatial working and reference memory to testosterone in males.…”

“…Thus, broad conclusions are more difficult to draw. In general, the bulk of evidence suggests that gonadectomy impairs memory in males tested in the radial arm maze, T-maze, Barnes Maze, and object recognition tasks, as well as several operant tasks that test prefrontal cortex function (Ceccarelli et al 2001;Kritzer et al 2001Kritzer et al , 2007Daniel et al 2003;Sandstrom et al 2006;Aubele et al 2008;Gibbs and Johnson 2008;Spritzer et al 2008;Locklear and Kritzer 2014). However, the deleterious effect of gonadectomy does not extend to all types of memory, particularly spatial reference memory tested in the Morris water maze (Gibbs 2005;Sandstrom et al 2006;Spritzer et al 2008).…”

Sex Hormones and Cognition: Neuroendocrine Influences on Memory and Learning

“…Chronic treatment in gonadectomized male rats with estradiol but not testosterone, enhanced spatial working memory in the radial arm maze, and improved learning in a delayed-match-to-position T-maze task (206,208,389). Estradiol also reversed gonadectomy-induced impairments in the Barnes Maze in adult male rats (379), a task in which performance is also improved by testosterone (379). However, longterm tonic estradiol administration (via pellets) did not reverse the gonadectomy-induced deficits in spatial alternation or several nonspatial prefrontal-cortex-mediated behaviors, whereas testosterone did reverse the deficits (347).…”