The Role of Androgen Receptors in Mediation of Nandrolone Effects on Spatial Memory and Neuronal Response of Pyramidal Neurons in the Hippocampal CA1 Area

Background: Previously we have reported that intracerebroventricular microinjection of nandrolone decanoate (ND) improves spatial memory and hippocampal synaptic plasticity, but the underlying mechanism has not been clearly evaluated. The aim of this study was evaluated the role of androgen receptors (ARs) in the mediation of ND effects on spatial memory and neuronal response of pyramidal neurons of the hippocampal CA1 area. Materials and Methods: In the current study, the rats were divided into four groups: the control group received DMSO, while other experimental groups received ND (60 μg/2.5 μL), nilutamide (5 μg/2.5 μL), and co-administration of nilutamide (5 μg/2.5 μL) + ND (60 μg/2.5 μL) for 4 days. Spatial learning and memory were evaluated through the Morris water maze (MWM) test. Moreover, we test the electrophysiological properties of hippocampal plasticity by in vitro field potential recordings. In electrophysiological investigations, the field excitatory postsynaptic potentials (fEPSPs) and population spikes were recorded from the hippocampal slices taken from different groups. Results: At the behavioral level, our studies exhibited that escape latency and traveled distance in ND-treated rats significantly decreased during the MWM test’s training period, whereas administration of nilutamide before ND had no significant effect on escape latency and traveled distance in the MWM task. Furthermore, the results of field potential recording showed that the magnitude of fEPSP-long-term potentiation (LTP) of the ND-treated group was higher than the control group, while preadministration of nilutamide abolished the ND improvement effect on the magnitude of fEPSP-LTP. Conclusion: This study suggests that the administration of ND induces improvement in spatial memory and hippocampal synaptic plasticity through activation of central ARs.