Organizational effects of testosterone on learning strategy preference and muscarinic receptor binding in prepubertal rats

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Prior to puberty, male rats, but not female rats, prefer a striatum-based stimulus-response learning strategy rather than a hippocampus-based place strategy on a water maze task that can be solved using either strategy. Neurochemically, learning strategy preference has been linked to the ratio of cholinergic muscarinic receptor binding in the hippocampus relative to the striatum, with lower ratios displayed by males compared to females and by stimulus-response learners compared to place learners. Sex differences in a variety of different behaviors are established by the organizational influence of testosterone on brain development. Therefore, the current study investigated the potential organizational effects of neonatal testosterone on learning strategy preference and the hippocampus:striatum ratio of muscarinic receptor binding in prepubertal male and female rats. Similar to vehicle-treated control males, prepubertal females treated with testosterone propionate on the first two days of life preferred a stimulus-response strategy on a dual-solution water maze task. Conversely, vehicle-treated prepubertal females were more likely to use a place strategy. Consistent with previous findings, the hippocampus:striatum ratio of muscarinic receptor binding was lower in rats preferring a stimulus-response strategy compared to those using a place strategy and lower in control males compared to control females. However, the hippocampus:striatum ratio was not reversed by neonatal testosterone treatment of females as predicted. The current study is the first to show that sex differences in how a navigational task is learned prior to puberty is impacted by the presence of testosterone during vulnerable periods in brain development.