Testosterone influences spatial strategy preferences among adult male rats

Abstract

Males outperform females on some spatial tasks, and this may be partially due to the effects of sex steroids on spatial strategy preferences. Previous work with rodents indicates that low estradiol levels bias females toward a striatum-dependent response strategy, whereas high estradiol levels bias them toward a hippocampus-dependent place strategy. We tested whether testosterone influenced the strategy preferences in male rats. All subjects were castrated and assigned to one of three daily injection doses of testosterone (0.125, 0.250, or 0.500 mg/rat) or a control group that received daily injections of the drug vehicle. Three different maze protocols were used to determine rats’ strategy preferences. A low dose of testosterone (0.125 mg) biased males toward a motor-response strategy on a T-maze task. In a water maze task in which the platform itself could be used intermittently as a visual cue, a low testosterone dose (0.125 mg) caused a significant increase in the use of a cued-response strategy relative to control males. Results from this second experiment also indicated that males receiving a high dose of testosterone (0.500 mg) were biased toward a place strategy. A third experiment indicated that testosterone dose did not have a strong influence on the ability of rats to use a nearby visual cue (floating ball) in the water maze. For this experiment, all groups seemed to use a combination of place and cued-response strategies. Overall, the results indicate that the effects of testosterone on spatial strategy preference are dose dependent and task dependent.

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

“…The comparable effects of supplementing GDX rats with TP or E suggest that the significant behavioral deficits induced in all of these domains by GDX stem at least in part from a loss of estrogen and/or estrogen metabolites. These findings contradict earlier studies from this lab where GDX-induced deficits in acquisition of T-maze (Kritzer et al, 2001) and operant spatial lever press tasks (Kritzer et al, 2007) were attenuated in GDX rats supplemented with TP but not with E. Although the dose and duration of hormone replacement have been shown to impact spatial cognition in GDX and gonadally intact male rats (Clark et al, 1995; Gibbs, 2005; Goudsmit et al, 1990; Spritzer et al, 2013), these factors were similar across studies and are thus unlikely to underlie the disparities in outcomes. Similarly, while Barnes maze testing has been shown to have minimal effects on rats' corticosterone levels (Harrison et al, 2009), rats in the prior studies were acclimated to handling, apparatus, and were subject to weeks-long testing, suggesting that cross-study differences in animals' stress responses may also have been minimal.…”

“…These include animals' ages (Bimonte-Nelson et al, 2003; Kanit et al, 2000) and hormone status, including the duration and dose of hormone deprivation and replacement (Bimonte and Denenberg, 1999; Daniel et al, 2006; Galea et al, 2001; Goudsmit et al, 1990; Spritzer et al, 2011; Spritzer et al, 2013). In addition, evidence for a male preference in utilization of hippocampal-dependent place strategies (Blokland et al, 2006; Hawley et al, 2012) and for high levels of testosterone in males and high levels of estrogen in proestrus females in biasing animals to use place rather than response strategies in solving spatial mazes (Korol et al, 2004; Spritzer et al, 2013) identify animals' approaches as yet another factor likely to influence outcomes, particularly across studies using mazes and testing contingencies where advantage is differentially conferred for place, response, or other strategies (Faraji et al, 2010; Gibbs and Johnson, 2008; Healy et al, 1999; Lund and Lephart, 2001; Ruprecht et al, 2013). …”

Sex differences in cognitive impairment and Alzheimer’s disease

“…Male rats castrated at pre-puberty period had lower levels of testosterone than sham-castrated rats and showed better spatial learning (shorter escape latency and traveled distance) than the sham-castrated males at the same age in MWM [55]. A low testosterone dose (0.125 mg) in castrated adult male rats caused a significant increase in the use of a cued-response strategy relative to control males [56]. While it is unclear whether testosterone directly regulates spatial learning, evidence suggested that optimal testosterone level affects spatial learning in males.…”

Testosterone regulates levels of cystic fibrosis transmembrane regulator, adenylate cyclase, and cAMP in the seminal vesicles of orchidectomized rats

“…Three weeks after orchidectomy, drugs were subcutaneously administered for seven (7) days behind the neck scruff. Testosterone doses were selected based as the previously reported doses [19,20]. Animals were divided into the following groups with n=6 per group: conditions.…”