Androgen modulates N-methyl-D-aspartate-mediated depolarization in CA1 hippocampal pyramidal cells

Previously, research elucidating steroid hormone actions in the central nervous system has focused on their role in sexual reproduction and maintaining homeostasis. The hippocampus is a target of steroid modulation and is involved in the development of emotional behavior and memory storage. Area CA1 of the hippocampus contains a high density of androgen receptor (AR) and N-methyl-D-aspartate (NMDA) receptors. NMDA receptors underlie excitatory synaptic transmission and excitotoxicity in CA1 neurons. The effects of AR activation on the neurophysiology of hippocampal pyramidal neurons is unknown. Standard intracellular recording techniques in hippocampal slices were used to investigate the effects of the non-aromatizable androgen, 5-alpha-dihydrotestos-terone-proprionate (DHTP), on CA1 pyramidal cell characteristics and NMDA receptor-mediated responses. Male Sprague-Dawley rats were unoperated, sham-operated (SHAM), gonadectomized (GDX), or gonadectomized with DHTP replacement therapy (GDX + DHTP). Neuronal AR was saturated by DHTP treatment as determined by binding studies and immunocytochemistry. Chronic DHTP treatment increased the action potential duration and decreased the fast afterhyperpolarization (fAHP) amplitude. To test the effect of DHTP on glutamate receptor-mediated responses, hippocampal slices were exposed to increasing concentrations of NMDA. In pyramidal cells from SHAM and GDX-treated animals, 30 microM NMDA induced an irreversible depolarization; the membrane potential of pyramidal cells from GDX + DHTP-treated animals recovered to baseline. The effect of DHTP was time dependent, implicating protein synthetic mechanisms. Our findings demonstrate that androgens can influence pyramidal cell characteristics and neurotransmitter-evoked actions in hippocampal CA1 pyramidal cells.