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

中隔海马胆碱能神经元在空间学习记忆功能中起重要作用。我们最近发现，在海马24小时乙酰胆碱（Ach）释放谱中存在显著的性别差异。实验一，为了研究性激素在海马24小时乙酰胆碱释放中的作用，在自由运动条件下，对完整大鼠、去性腺（Gdx）大鼠、去性腺睾酮（Gdx+T）大鼠和去性腺雌二醇-17β (Gdx+E)大鼠进行体内微透析研究。每隔20分钟从海马背侧收集透析液，同时监测同一受试者的自发运动活动。虽然在完整雄性和循环雌性大鼠中观察到不同性别的乙酰胆碱释放，但在Gdx大鼠的两性中，黑暗期乙酰胆碱释放严重减弱。Gdx+T雄性大鼠和Gdx+E雌性大鼠均能成功地恢复黑暗过程中乙酰胆碱的释放，而Gdx+T雌性大鼠和Gdx+E雄性大鼠均不能恢复这两个特征。虽然Gdx显著降低了乙酰胆碱释放与自发性运动活动的相关系数，但Gdx+T雄性大鼠和Gdx+E雌性大鼠均成功恢复了相关系数。实验二，为进一步研究性激素对海马内乙酰胆碱释放的短期影响，分别在Gdx雄性大鼠和Gdx雌性大鼠皮下注射睾酮（2 mg）或雌二醇-17β (40 μg)。睾酮注射对Gdx雄性大鼠的作用是逐渐的，但在最初几个小时内乙酰胆碱释放明显增加，在10小时内使乙酰胆碱释放恢复到正常雄性大鼠的水平。同样，雌二醇-17β注射在Gdx雌性大鼠中也能在最初几小时内增加乙酰胆碱释放，并在10小时内恢复到循环雌性大鼠的水平。注油对乙酰胆碱释放无明显影响。目前的研究结果表明：(1)雄性大鼠的睾酮和雌性大鼠的雌二醇-17β对维持海马中乙酰胆碱释放的正常特征至关重要；(2)性激素可能对乙酰胆碱释放有短期影响。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