Prelimbic of Medial Prefrontal Cortex GABA Modulation through Testosterone on Spatial Learning and Memory

Prefrontal cortex (PFC) is involved in multiple functions including attentional processes, spatial orientation, short-term memory, and long-term memory. Our previous study indicated that microinjection of testosterone in CA1 impaired spatial learning and memory. Some evidence suggests that impairment effect of testosterone is mediated by GABAergic system. In the present study, we investigated the interaction of testosterone (androgenic receptor agonist) and bicuculline (GABA_A receptor antagonist) on spatial learning and memory performance in the prelimbic (PL) of male Wistar rats. Cannulae were bilaterally implanted into the PL region of PFC and drugs were daily microinjected for two minutes in each side. There are 4 experiments. In the first experiment, three sham groups were operated (solvent of testosterone, bicuculline, testosterone plus bicuculline). In the second experiment, different doses of testosterone (40, 80 μg /0.5 μL DMSO/each side) were injected into the PL before each session. In the third experiment, intra PL injections of bicuculline (2, 4 μg/0.5 μL DMSO/each side) were given before every session. In the last experiment, testosterone (80μg/0.5 μL DMSO/each side) along with bicuculline (2 μg/0.5 μL DMSO/each side) was injected into the PL. The results showed there is no difference between control group and sham operated group. Testosterone 80 μg and bicuculline 2 μg, each given separately, and also in combination increased escape latency to find the platform compared to the sham operated and cause to impaired spatial learning and memory. It is shown that intra PL microinjection of bicuculline after testosterone treatment could not rescue the spatial learning and memory impaired induced by testosterone.