Androgens’ performance-enhancing effects in the inhibitory avoidance and water maze tasks may involve actions at intracellular androgen receptors in the dorsal hippocampus

Androgens can have performance-enhancing effects in some cognitive tasks, but the mechanism of these effects has not been established. Experiments examined whether androgens’ actions to bind to intracellular androgen receptors (ARs) in the hippocampus are necessary to enhance cognitive performance in the inhibitory avoidance and water maze tasks. If androgens’ binding at ARs are essential, then blocking them through intrahippocampal administration of flutamide, an AR receptor antagonist, should attenuate androgens’ performance-enhancing effects in the inhibitory avoidance and water maze tasks. In Experiments 1 and 2, flutamide was administered through intrahippocampal inserts to intact male rats immediately pre- and post-training in the inhibitory avoidance and water maze tasks. Both pre- and post-training administration of flutamide to the dorsal hippocampus, but not missed sites, produced significantly poorer performance in the inhibitory avoidance and water maze tasks, without influencing control measures such as flinch/jump threshold or swim speed. In Experiment 3, flutamide administration to the hippocampus was delayed two hours following training in the inhibitory avoidance and water maze tasks. There was no significant effect of delayed administration of flutamide on performance in either of these tasks. Together, these findings suggest that blocking ARs in the dorsal hippocampus with flutamide administration immediately pre- or post-training can produce decrements in cognitive performance, which implies that androgens’ performance-enhancing effects may occur, in part, through binding at intracellular androgen receptors in the dorsal hippocampus.