The astrocytic glutamate transporter GLT-1 performs glutamate uptake thereby mediating NMDAr responses in neurons. Ceftriaxone (CEF) upregulates astrocytic GLT-1 expression/activity, which could counteract excessive glutamate levels and aggressive behavior induced by anabolic synthetic steroids such as nandrolone decanoate (ND). Here, adult male CF-1 mice were allocated to oil (VEH), ND, CEF, and ND/CEF groups. Mice were subcutaneously (s.c.) injected with ND (15 mg/kg) or VEH for 19 days, and received intraperitoneal (i.p.) injections of CEF (200 mg/kg) or saline for 5 days. The ND/CEF group received ND for 19 days plus coadministration of CEF in the last 5 days. On the 19th day, the aggressive phenotypes were evaluated through the resident-intruder test. After 24 h, cerebrospinal fluid was collected to measure glutamate levels, and the pre-frontal cortex was used to assess GLT-1, pGluN2B^Tyr1472, and pGluN2A^Tyr1246 by Western blot. Synaptosomes from the left brain hemisphere was used to evaluate mitochondrial function including complex II-succinate dehydrogenase (SDH), Ca²⁺ handling, membrane potential (ΔѰ_m), and H₂O₂ production. ND decreased the latency for the first attack and increased the number of attacks by the resident mice against the intruder, mechanistically associated with an increase in glutamate levels and pGluN2B^Tyr1472 but not pGluN2A^Tyr1244, and GLT-1 downregulation. The abnormalities in mitochondrial Ca²⁺ influx, SDH, ΔѰ_m, and H₂O₂ implies in deficient energy support to the synaptic machinery. The ND/CEF group displayed a decreased aggressive behavior, normalization of glutamate and pGluN2B^Tyr1472levels, and mitochondrial function at synaptic terminals. In conclusion, the pharmacological modulation of GLT-1 highlights its relevance as an astrocytic target against highly impulsive and aggressive phenotypes.

星形细胞谷氨酸转运蛋白GLT-1执行谷氨酸摄取，从而介导神经元中的NMDAR反应。头孢曲松钠（CEF）上调星形细胞GLT-1的表达/活性，这可以抵消合成代谢类固醇如癸酸诺龙（ND）诱导的过量谷氨酸水平和侵略性行为。在这里，成年男性CF将-1只小鼠分为油（VEH），ND，CEF和ND / CEF组。给小鼠皮下注射（sc）ND（15 mg / kg）或VEH 19天，并接受腹腔（ip）CEF（200 mg / kg）或生理盐水注射5天。ND / CEF小组接受了为期19天的ND，并在过去5天内共同接受了CEF。在第19天，通过常驻入侵者测试评估攻击性表型。24小时后，收集脑脊液以测量谷氨酸水平，并通过Western印迹将前额叶皮层用于评估GLT-1，pGluN2B ^Tyr1472和pGluN2A ^Tyr1246。来自左脑半球的突触小体用于评估线粒体功能，包括复杂的II-琥珀酸脱氢酶（SDH），Ca ²⁺处理，膜电位（ΔѰ_米），和H ₂ ö ₂的生产。ND降低了延迟的第一次进攻，并通过对入侵者的居民老鼠，机械地与增加谷氨酸含量和pGluN2B与增加的攻击次数^Tyr1472但不pGluN2A ^Tyr1244和GLT-1下调。线粒体的Ca异常²⁺内流，SDH，ΔѰ_米，和H ₂ ö ₂意味着在以突触机械缺陷能量的支持。ND / CEF组的攻击行为降低，谷氨酸和pGluN2B ^{Tyr1472正常化}水平和突触末端的线粒体功能。总之，GLT-1的药理学调节突显了其作为针对高度冲动和攻击性表型的星形细胞靶标的相关性。