Le Grevès P, Zhou Q, Huang W, Nyberg F
Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, Uppsala University, Uppsala, Sweden.
Acta Psychiatr Scand Suppl. 2002(412):129-32. doi: 10.1034/j.1600-0447.106.s412.28.x.
Anabolic androgenic steroids (AAS) have been suggested to sensitize mechanisms involved in drug dependency and aggressive behaviour. Nucleus accumbens and periaqueductal gray (PAG) are believed to be critical in the functional anatomy of these two phenomena, which are partly mediated by the NMDA receptor. This study was undertaken in order to determine the relationship between the effect of AAS and cocaine (given alone or in combination) on the gene expression of the NMDA receptor subtype NR1 in the rat nucleus accumbens and PAG.
Male rats were subjected to 2 weeks of daily doses of cocaine and the anabolic-androgenic steroid nandrolone, administrated separately or in combination, and the effect on the mRNA expression for the NMDA receptor NR1 subunit was studied by Northern blot analysis.
In the nucleus accumbens, injection of cocaine alone and the combination of cocaine and nandrolone caused a significant decrease in the NR1 mRNA level compared with that of control rats. The combined treatment significantly down-regulated the transcript in the PAG compared with the groups injected with vehicle, nandrolone or cocaine alone.
It was concluded that AAS combined with cocaine may induce additive increases in glutamatergic activity in these brain areas, supporting the notion that these steroids can sensitize mechanisms involved in the reward and the expression of aggression.
有研究表明，合成代谢雄激素类固醇（AAS）会使与药物依赖和攻击行为相关的机制敏感化。伏隔核和导水管周围灰质（PAG）被认为在这两种现象的功能解剖学中起关键作用，这两种现象部分由N-甲基-D-天冬氨酸（NMDA）受体介导。本研究旨在确定AAS和可卡因（单独或联合使用）对大鼠伏隔核和PAG中NMDA受体亚型NR1基因表达的影响之间的关系。
对雄性大鼠每日分别或联合给予可卡因和合成代谢雄激素类固醇诺龙，持续2周，通过Northern印迹分析研究其对NMDA受体NR1亚基mRNA表达的影响。
在伏隔核中，与对照大鼠相比，单独注射可卡因以及可卡因和诺龙联合注射均导致NR1 mRNA水平显著降低。与单独注射溶剂、诺龙或可卡因组相比，联合治疗显著下调了PAG中的转录本。
得出的结论是，AAS与可卡因联合使用可能会使这些脑区的谷氨酸能活性增加，这支持了这些类固醇会使与奖赏和攻击行为表达相关的机制敏感化的观点。
