Center for Safety Pharmacology, Korea Institute of Toxicology, Daejeon 305-343, Republic of Korea.
Neurosci Lett. 2013 Oct 25;555:198-202. doi: 10.1016/j.neulet.2013.09.029. Epub 2013 Sep 26.
We have previously demonstrated that saikosaponin A (SSA) attenuated morphine self-administration behavior. In the present study, we evaluated the effects of SSA on cocaine-maintained responding using self-administration procedure. Rats self-administered cocaine (0.25mg/kg per infusion) under a fixed ratio 1 schedule of reinforcement during daily 3-h session. Once stable basal responses were obtained, rats were pretreated with each doses of SSA (1.0, 2.5, 5.0mg/kg) or its vehicle (5% Tween-80) by an intraperitoneal injection 30min before the start of self-administration testing. Additionally, different groups of rats received either the selective GABAB antagonist SCH 50911 or the GABAA antagonist bicuculline before systemic administration of SSA at dose of 2.5mg/kg. Results showed that SSA significantly reduced cocaine self-administration without affecting food consumption. SSA inhibition of cocaine reinforced-responding was blocked by SCH 50911, but not bicuculline. Results suggest that SSA may attenuate cocaine-reinforced behavior through activation of GABAB receptors.
我们之前已经证明柴胡皂苷 A (SSA) 可以减轻吗啡的自我给药行为。在本研究中，我们使用自我给药程序评估了 SSA 对可卡因维持反应的影响。大鼠在每日 3 小时的时间段内，根据固定比率 1 强化程序自我给予可卡因（每次输注 0.25mg/kg）。一旦获得稳定的基础反应，大鼠在开始自我给药测试前 30 分钟通过腹腔注射接受 SSA 的每个剂量（1.0、2.5、5.0mg/kg）或其载体（5%吐温-80）预处理。此外，不同组的大鼠在给予 2.5mg/kg 的 SSA 之前接受了选择性 GABA B 拮抗剂 SCH 50911 或 GABA A 拮抗剂荷包牡丹碱的处理。结果表明，SSA 可显著减少可卡因的自我给药，而不影响食物消耗。SCH 50911 阻断了 SSA 对可卡因强化反应的抑制作用，但荷包牡丹碱没有。结果表明，SSA 可能通过激活 GABA B 受体来减轻可卡因强化行为。
