Triemstra Jennifer L, Sato Satoru M, Wood Ruth I
Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, 1333 San Pablo St., BMT 401, Los Angeles, CA 90033, USA.
Psychoneuroendocrinology. 2008 Apr;33(3):386-94. doi: 10.1016/j.psyneuen.2007.12.006. Epub 2008 Jan 30.
Most drugs of abuse increase dopamine (DA) in nucleus accumbens (Acb). However, the effects of anabolic androgenic steroids (AAS) on Acb DA have not been examined. We determined the effects of subcutaneous (sc) testosterone (T) on Acb DA in male hamsters. The effects of sc amphetamine were also examined for comparison. In addition, Acb DA was evaluated during intracerebroventricular (ICV) T infusion, designed to mimic T intake during ICV T self-administration in drug-naïve and drug-preexposed animals. Acb DA was measured using in vivo microdialysis and HPLC-EC. T (7.5 or 37.5 mg/kg), amphetamine (1 or 5 mg/kg), or vehicle was injected sc and Acb DA monitored for 4h. In the ICV experiment, T (1 or 2 microg/infusion) or vehicle was infused ICV every 6 min for 4h and Acb DA monitored. ICV T preexposure was accomplished by repeating the same ICV T infusion (1 microg/infusion) daily for 14 days, and T infusion was accompanied by microdialysis on 15th day. Neither sc nor ICV T administration increased Acb DA. At high dose (2 microg/infusion), ICV T decreased Acb DA. Likewise, daily ICV infusion of T for 15 days did not alter Acb DA. In contrast, sc amphetamine significantly increased Acb DA at both doses. Therefore, unlike many drugs of abuse, AAS does not increase Acb DA levels. The reduction in DA at high T doses is likely due to autonomic depressant effects of AAS. We suggest that AAS act via mechanism distinct from those of stimulants, but may share neural substrates with other drugs of abuse.
大多数滥用药物会增加伏隔核（Acb）中的多巴胺（DA）。然而，合成代谢雄激素类固醇（AAS）对Acb中DA的影响尚未得到研究。我们确定了皮下注射（sc）睾酮（T）对雄性仓鼠Acb中DA的影响。为作比较，还研究了皮下注射苯丙胺的影响。此外，在脑室内（ICV）注射T期间评估了Acb中的DA，此设计旨在模拟未接触过药物和曾接触过药物的动物在ICV T自我给药期间的T摄入情况。使用体内微透析和高效液相色谱 - 电化学检测法测量Acb中的DA。皮下注射T（7.5或37.5 mg/kg）、苯丙胺（1或5 mg/kg）或溶剂，并监测Acb中DA 4小时。在ICV实验中，每6分钟脑室内注射T（1或2μg/次）或溶剂，持续4小时，并监测Acb中DA。通过每天重复相同的ICV T注射（1μg/次），持续14天来实现ICV T预先接触，在第15天进行T注射并同时进行微透析。皮下注射或脑室内注射T均未增加Acb中的DA。在高剂量（2μg/次）时，脑室内注射T会降低Acb中的DA。同样，连续15天每天脑室内注射T也未改变Acb中的DA。相比之下，皮下注射苯丙胺在两种剂量下均显著增加了Acb中的DA。因此，与许多滥用药物不同，AAS不会增加Acb中的DA水平。高剂量T导致DA减少可能是由于AAS的自主神经抑制作用。我们认为AAS的作用机制与兴奋剂不同，但可能与其他滥用药物共享神经底物。
