Dose-dependent effects of testosterone on spatial learning strategies and brain-derived neurotrophic factor in male rats

Abstract

Studies suggest that males outperform females on some spatial tasks. This may be due to the effects of sex steroids on spatial strategy preferences. Past experiments with male rats have demonstrated that low doses of testosterone bias them toward a response strategy, whereas high doses of testosterone bias them toward a place strategy. We investigated the effect of different testosterone doses on the ability of male rats to effectively employ these two spatial learning strategies. Furthermore, we quantified concentrations of brain-derived neurotrophic factor (pro-, mature-, and total BDNF) in the prefrontal cortex, hippocampus, and striatum. All rats were bilaterally castrated and assigned to one of three daily injection doses of testosterone propionate (0.125, 0.250, or 0.500 mg/rat) or a control injection of the drug vehicle. Using a plus-maze protocol, we found that a lower testosterone dose (0.125 mg) significantly improved rats’ performance on a response task, whereas a higher testosterone dose (0.500 mg) significantly improved rats’ performance on a place task. In addition, we found that a low dose of testosterone (0.125 mg) increased total BDNF in the striatum, while a high dose (0.500 mg) increased total BDNF in the hippocampus. Taken altogether, these results suggest that high and low levels of testosterone enhance performance on place and response spatial tasks, respectively, and this effect is associated with changes in BDNF levels within relevant brain regions.