van den Buuse Maarten, Sun Jenny, Gogos Andrea
School of Psychology and Public Health, La Trobe University, Melbourne, Australia.
School of Psychology and Public Health, La Trobe University, Melbourne, Australia; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia.
Horm Behav. 2025 Jan;167:105673. doi: 10.1016/j.yhbeh.2024.105673. Epub 2024 Dec 24.
The aim of the present study was to investigate the role of ovarian hormones on dopaminergic regulation of prepulse inhibition (PPI), a measure of sensorimotor gating deficient in schizophrenia and other psychiatric illnesses. Either in adulthood (11 weeks of age) or adolescence (5 weeks of age), female mice underwent ovariectomy (OVX) and were implanted with 17β-estradiol, progesterone, or a combination of these hormones. All mice were tested in adulthood for the acute effect of the dopamine receptor agonist, apomorphine, on PPI. Apomorphine treatment reduced PPI in intact mice and this effect was blocked after OVX in adulthood. A low dose implant of 17β-estradiol prevented this OVX effect and reinstated apomorphine-induced PPI disruption. Following adolescent OVX, the effect of apomorphine was not altered and it significantly reduced PPI in adulthood. A low dose implant of 17β-estradiol following adolescent OVX effect blocked apomorphine-induced PPI disruption in adulthood. Apomorphine had no effect on PPI in any of the mice treated with the high dose of 17β-estradiol or a combination of low-dose 17β-estradiol and progesterone, irrespective of treatment age, suggesting an antipsychotic action. Apomorphine tended to disrupt PPI in mice treated with progesterone only, irrespective of age of OVX. These results suggest that in adult mice, circulating 17β-estradiol and progesterone play an important role in dopaminergic regulation of PPI. This role may develop during adolescence as similar effects of OVX and ovarian hormones were not observed following interventions in 5-week old mice. Our results also confirm and extend previous evidence that 17β-estradiol may have antipsychotic properties.
本研究的目的是调查卵巢激素在多巴胺能调节前脉冲抑制（PPI）中的作用，PPI是精神分裂症和其他精神疾病中感觉运动门控缺陷的一种测量指标。成年（11周龄）或青春期（5周龄）的雌性小鼠接受卵巢切除术（OVX），并植入17β-雌二醇、孕酮或这些激素的组合。所有小鼠在成年期接受测试，以检测多巴胺受体激动剂阿扑吗啡对PPI的急性影响。阿扑吗啡治疗降低了完整小鼠的PPI，成年期OVX后这种作用被阻断。低剂量植入17β-雌二醇可预防这种OVX效应，并恢复阿扑吗啡诱导的PPI破坏。青春期OVX后，阿扑吗啡的作用未改变，且在成年期显著降低了PPI。青春期OVX后低剂量植入17β-雌二醇可阻断成年期阿扑吗啡诱导的PPI破坏。无论治疗年龄如何，阿扑吗啡对高剂量17β-雌二醇或低剂量17β-雌二醇与孕酮组合治疗的任何小鼠的PPI均无影响，提示具有抗精神病作用。无论OVX年龄如何，阿扑吗啡倾向于破坏仅用孕酮治疗的小鼠的PPI。这些结果表明，在成年小鼠中，循环中的17β-雌二醇和孕酮在PPI的多巴胺能调节中起重要作用。这种作用可能在青春期发展，因为在5周龄小鼠中进行干预后未观察到OVX和卵巢激素的类似作用。我们的结果还证实并扩展了先前的证据，即17β-雌二醇可能具有抗精神病特性。
