Department of Alcohol, Drugs and Addiction, National Institute for Health and Welfare, Helsinki, Finland.
Pharmacol Biochem Behav. 2010 Jun;95(4):422-7. doi: 10.1016/j.pbb.2010.02.020. Epub 2010 Mar 6.
Previously we have reported that sub-chronic administration of nandrolone modifies reward-related neurochemical effects of psychomotor stimulant drugs of abuse. The aim of the present study was to evaluate whether the ability of nandrolone (19-nortestosterone) to attenuate the effects of amphetamine depends on activation of androgen (AR) or estrogen receptors (ER). We used an in vivo microdialysis technique in fully conscious rats to monitor whether administration of the AR-antagonist flutamide (7x50 mg/kg) or the ER-antagonist clomiphene (7x20 mg/kg), attenuates nandrolone-induced modulation of dopaminergic and serotonergic effects of acute injections of amphetamine (1 mg/kg). Dopamine (DA), 5-hydroxytryptamine (5-HT) and their metabolites were measured from the samples using high performance liquid chromatography (HPLC). Blocking the androgen receptors with flutamide abolished the attenuating effect of nandrolone pre-treatment on amphetamine-induced elevation of extracellular DA concentration. Blocking the estrogen receptors with clomiphene did the same but to a lesser extent. In conclusion, the results of this study show that the ability of nandrolone to attenuate the effects of amphetamine depends on activation of androgen receptors or to a lesser extent, on estrogen receptors.
先前我们已经报道过，去甲雄酮的亚慢性给药可改变滥用的精神兴奋剂药物的奖赏相关神经化学效应。本研究的目的是评估去甲雄酮（诺龙）减弱安非他命效应的能力是否依赖于雄激素（AR）或雌激素受体（ER）的激活。我们使用在体微透析技术在完全清醒的大鼠中监测雄激素拮抗剂氟他胺（7x50 mg/kg）或雌激素拮抗剂氯米芬（7x20 mg/kg）的给药是否会减弱去甲雄酮对急性注射安非他命（1 mg/kg）引起的多巴胺能和 5-羟色胺能效应的调制。使用高效液相色谱法（HPLC）从样品中测量多巴胺（DA）、5-羟色胺（5-HT）及其代谢物。用氟他胺阻断雄激素受体消除了去甲雄酮预处理对安非他命引起的细胞外 DA 浓度升高的抑制作用。用氯米芬阻断雌激素受体也有同样的效果，但程度较轻。总之，这项研究的结果表明，去甲雄酮减弱安非他命效应的能力依赖于雄激素受体的激活，或在较小程度上依赖于雌激素受体的激活。
