Role of gonadal steroids on the in vivo acetylcholine release in the hippocampus

隔-海马胆碱能神经元在空间学习记忆功能中起着重要作用。我们最近发现，海马区24小时乙酰胆碱(Ach)的释放情况存在显著的性别差异。为探讨性激素在大鼠海马区24 h ACh释放中的作用，在自由活动条件下，对正常大鼠、去性腺(Gdx)大鼠、去势睾酮(Gdx+T)大鼠和去性腺雌二醇-17β(Gdx+E)大鼠进行了体内微透析研究。每隔20分钟从背侧海马区收集透析液，同时监测同一受试者的自发活动。尽管在正常雄性和周期雌性大鼠中观察到了特定性别的ACh释放谱，但在GDX大鼠中，暗期ACh的释放在两性中都严重减弱。GDX+T雄性大鼠和GDX+E雌性大鼠均成功地恢复了暗时相…中ACh的释放而GDX+T雌性大鼠和GDX+E雄性大鼠均未恢复各自的形态。虽然GDX显著降低了ACh释放与自发活动的相关系数，但GDX+T雄性大鼠和GDX+E雌性大鼠均成功地恢复了相关系数。实验二，为进一步探讨性激素对大鼠海马区ACh释放的短期影响，分别给雄性和雌性大鼠皮下注射睾酮(2 Mg)或雌二醇-17β(40μg)。GDX雄性大鼠注射睾酮后，ACh释放逐渐增加，但在最初几小时内显著增加，并在10h内恢复至正常雄性大鼠水平。雌性GDX大鼠注射17雌二醇β后，ACh释放量在最初的几小时内也明显增加，10小时内恢复到雌性大鼠的水平。注油对ACh释放量无明显影响。目前的结果表明：(1)雄性大鼠的睾酮和雌性大鼠的雌二醇-17β是维持海马区ACh释放的正常模式所必需的；(2)性激素可能对ACh的释放有短期影响。较少

Septo-hippocampal cholinergic neurons play a significant role in the spatial learning and memory function. We recently revealed a marked sex difference in the profile of 24-h acetylcholine (Ach) release in the hippocampus. In experiment I, to examine the role of sex hormones in the 24-h ACh release in the hippocampus, in vivo microdialysis study was performed in intact, gonadectomized (Gdx), gonadectomized testosterone-primed (Gdx+T), and gonadectomized estadiol-17β-primed (Gdx+E) rats, under the freely moving condition for more than 24 hours. The dialysate was collected from the dorsal hippocampus at 20-min intervals, and spontaneous locomotor activity was simultaneously monitored in the same subject. Although the sex-specific ACh release profile was observed in intact male and cycling female rats, the ACh release during the dark phase was severely attenuated in both sexes of Gdx rats. Both Gdx+T male rats and Gdx+E female rats successfully restored the ACh release during the dark pha … More se, while neither Gdx+T female rats nor Gdx+E male rats restored each profile. Although Gdx significantly decreased in the correlation coefficient between the ACh release and the spontaneous locomotor activity, both Gdx+T male rats and Gdx+E female rats successfully restored the correlation coefficient. In experiment II, to further examine the short-term effect of sex hormones on the ACh release in the hippocampus, testosterone (2 mg) or estadiol-17β (40 μg) was subcutaneously injected in Gdx male and Gdx female rats, respectively. Testosterone injection in Gdx male rats gradually, but significantly increased the ACh release within the first few hours, and it restored the ACh release up to the level in intact male rats within 10 hours. Similarly, estradiol-17β injection in Gdx female rats also increased the ACh release within the first few hours, and restored the ACh release up to the level in cycling female rats within 10 hours. Oil injection showed no significant effects on the ACh release. Present results demonstrated that (1) testosterone in male rats as well as estadiol-17β in female rats are essential to maintain the normal profile of ACh release in the hippocampus, (2) sex hormones may have a short-term effect on the ACh release. Less