Anorexia nervosa (AN) is a mental illness with the highest rates of mortality and relapse, and no approved pharmacological treatment. Using an animal model of AN, called activity-based anorexia (ABA), we showed earlier that a single intraperitoneal injection of ketamine at a dose of 30 mg/kg (30mgKET), but not 3 mg/kg (3mgKET), has a long-lasting effect upon adolescent females of ameliorating anorexia-like symptoms through the following changes: enhanced food consumption and body weight; reduced running and anxiety-like behavior. However, there were also individual differences in the drug's efficacy. We hypothesized that individual differences in ketamine's ameliorative effects involve drebrin A, an F-actin-binding protein known to be required for the activity-dependent trafficking of NMDA receptors (NMDARs). We tested this hypothesis by electron microscopic quantifications of drebrin A immunoreactivity at excitatory synapses of pyramidal neurons (PN) and GABAergic interneurons (GABA-IN) in deep layer 1 of prefrontal cortex (PFC) of these mice. Results reveal that (1) the areal density of excitatory synapses on GABA-IN is greater for the 30mgKET group than the 3mgKET group; (2) the proportion of drebrin A+ excitatory synapses is greater for both PN and GABA-IN of 30mgKET than 3mgKET group. Correlation analyses with behavioral measurements revealed that (3) 30mgKET's protection is associated with reduced levels of drebrin A in the cytoplasm of GABA-IN and higher levels at extrasynaptic membranous sites of PN and GABA-IN; (5) altogether pointing to 30mgKET-induced homeostatic plasticity that engages drebrin A at excitatory synapses of both PN and GABA-IN.

中文翻译：

---

在神经性厌食症雌性小鼠模型中，青少年氯胺酮治疗的积极结果的个体差异涉及内侧前额叶皮质兴奋性突触的 drebrin A

神经性厌食症 (AN) 是一种死亡率和复发率最高的精神疾病，目前尚无批准的药物治疗方法。使用 AN 的动物模型，称为基于活动的厌食症 (ABA)，我们早些时候表明，单次腹膜内注射氯胺酮的剂量为 30 mg/kg (30mgKET)，但不是 3 mg/kg (3mgKET)，具有通过以下变化对青春期女性产生长期的厌食样症状改善作用：增加食物消耗和体重；减少跑步和类似焦虑的行为。但是，药物的疗效也存在个体差异。我们假设氯胺酮改善作用的个体差异涉及 drebrin A，这是一种 F-肌动蛋白结合蛋白，已知是 NMDA 受体 (NMDAR) 活性依赖性运输所必需的。我们通过对这些小鼠前额叶皮层 (PFC) 深层 1 中锥体神经元 (PN) 和 GABA 能中间神经元 (GABA-IN) 兴奋性突触的 drebrin A 免疫反应性进行电子显微镜定量来检验这一假设。结果表明：(1) 30mgKET 组的 GABA-IN 兴奋性突触面密度大于 3mgKET 组；(2) 30mgKET 组的 PN 和 GABA-IN 的 drebrin A+ 兴奋性突触比例均高于 3mgKET 组。与行为测量的相关性分析表明，(3) 30mgKET 的保护作用与 GABA-IN 细胞质中 drebrin A 水平降低以及 PN 和 GABA-IN 突触外膜位点水平升高有关；