Gholaminejad Azadeh, Gholamipour-Badie Hamid, Nasehi Mohammad, Naghdi Nasser
Department of Physiology and Pharmacology, Pasteur Institute of Iran (IPI), Tehran, Iran.
Department of Cognitive Neuroscience, Institute for Cognitive Science Studies (ICSS), Tehran, Iran.
Iran J Pharm Res. 2019 Summer;18(3):1429-1444. doi: 10.22037/ijpr.2019.1100745.
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 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.
前额叶皮质（PFC）参与多种功能，包括注意力过程、空间定向、短期记忆和长期记忆。我们之前的研究表明，在CA1区微量注射睾酮会损害空间学习和记忆。一些证据表明，睾酮的损害作用是由GABA能系统介导的。在本研究中，我们研究了睾酮（雄激素受体激动剂）和荷包牡丹碱（GABA受体拮抗剂）对雄性Wistar大鼠前边缘区（PL）空间学习和记忆表现的相互作用。将套管双侧植入PFC的PL区域，每天在每侧微量注射药物两分钟。共有4个实验。在第一个实验中，对三个假手术组进行操作（睾酮溶剂、荷包牡丹碱、睾酮加荷包牡丹碱）。在第二个实验中，在每次实验前向PL区注射不同剂量的睾酮（40、80μg/0.5μL二甲基亚砜/每侧）。在第三个实验中，在每次实验前向PL内注射荷包牡丹碱（2、4μg/0.5μL二甲基亚砜/每侧）。在最后一个实验中，将睾酮（80μg/0.5μL二甲基亚砜/每侧）与荷包牡丹碱（2μg/0.5μL二甲基亚砜/每侧）注射到PL中。结果显示，对照组和假手术组之间没有差异。与假手术组相比，单独给予80μg睾酮和2μg荷包牡丹碱，以及联合给予时，找到平台的逃避潜伏期增加，导致空间学习和记忆受损。结果表明，睾酮处理后向PL内微量注射荷包牡丹碱不能挽救睾酮诱导的空间学习和记忆损伤。
