Seaver Autism Center for Research and Treatment , Icahn School of Medicine at Mount Sinai , New York , New York 10029 , United States.
ACS Chem Neurosci. 2019 Oct 16;10(10):4213-4220. doi: 10.1021/acschemneuro.9b00309. Epub 2019 Sep 11.
Addiction to psychostimulants is a major public health crisis that leads to significant morbidity and mortality, for which there are currently no FDA-approved pharmacotherapies. Female subjects have increased propensity to develop pathological substance use disorders after initial use, suggesting the possibility of different pathophysiological mechanisms between males and females. Recently, we identified the neuroactive cytokine granulocyte-colony stimulating factor (G-CSF) as a key mediator of neuronal and behavioral plasticity in response to cocaine in male mice. Here, we found that G-CSF potentiated the rewarding effects of cocaine in female mice as well; however, the dopaminergic mechanism linked to these effects was highly dependent on the ovarian hormone cycle. G-CSF treatment enhanced the ability of cocaine to inhibit dopamine clearance; however, this effect was observed specifically during pro/estrus, when circulating ovarian hormone levels were high. These findings demonstrate important sex differences in the synaptic effects of this translationally relevant neuroimmune modulator.
对精神兴奋剂的依赖是一个主要的公共健康危机，导致了大量的发病率和死亡率，目前还没有 FDA 批准的药物治疗方法。女性在初次使用后更容易患上病理性物质使用障碍，这表明男性和女性之间可能存在不同的病理生理机制。最近，我们发现神经活性细胞因子粒细胞集落刺激因子 (G-CSF) 是雄性小鼠对可卡因产生神经元和行为可塑性反应的关键介质。在这里，我们发现 G-CSF 也增强了可卡因对雌性小鼠的奖赏作用;然而，与这些作用相关的多巴胺能机制高度依赖于卵巢激素周期。G-CSF 治疗增强了可卡因抑制多巴胺清除的能力;然而，这种效应仅在发情前期观察到，此时循环卵巢激素水平较高。这些发现表明，这种具有转化相关性的神经免疫调节剂在突触效应上存在重要的性别差异。
