Lorrai Irene, Maccioni Paola, Carai Mauro A M, Capra Alessandro, Castelli M Paola, Riva Antonella, Morazzoni Paolo, Gessa Gian Luigi, Colombo Giancarlo
Neuroscience Institute, National Research Council of Italy, Section of Cagliari, I-09042 Monserrato, CA, Italy.
Cagliari Pharmacological Research s.r.l., I-09127 Cagliari, CA, Italy.
Neurosci Lett. 2017 Jan 18;638:211-217. doi: 10.1016/j.neulet.2016.12.019. Epub 2016 Dec 19.
Recent lines of experimental evidence have indicated that saikosaponin A (SSA) - a bioactive ingredient of the medicinal plant, Bupleurum falcatum L. - suppressed alcohol, morphine, and cocaine self-administration in rats. The present paper was designed to assess whether the protective properties of SSA on addiction-related behaviors generalize to a hyperpalatable food such as a chocolate-flavored beverage (CFB). To this end, rats were initially trained to lever-respond for CFB [5% (w/v) Nesquik powder in water] under fixed ratio (FR) 10 (FR10) schedule of reinforcement. Once lever-responding reached stable levels, rats were treated acutely with two different dose ranges of SSA (0, 0.25, 0.5, and 1mg/kg; 0, 1, 2.5, and 5mg/kg; i.p.) and exposed to the FR10 and progressive ratio (PR) schedules of reinforcement in four independent experiments. The effect of acutely administered SSA (0, 0.25, 0.5, and 1mg/kg; i.p.) on cue-induced reinstatement of seeking behavior for CFB was also assessed. Under the FR and PR schedules of reinforcement, treatment with SSA diminished lever-responding for CFB, amount of self-administered CFB, and breakpoint for CFB. All variables were virtually completely suppressed after treatment with 5mg/kg SSA. Treatment with SSA also suppressed reinstatement of CFB-seeking behavior. No dose of SSA altered rat motor-performance, evaluated exposing all rats to an inverted screen test immediately after the self-administration session. These results demonstrate that acute treatment with SSA potently suppressed several addictive-like behaviors motivated by highly hedonic nourishment. These data extend to a highly rewarding natural stimulus the anti-addictive properties of SSA recently disclosed in rats self-administering alcohol, morphine, and cocaine.
最近一系列实验证据表明，柴胡皂苷A（SSA）——药用植物柴胡的一种生物活性成分——可抑制大鼠的酒精、吗啡和可卡因自我给药行为。本文旨在评估SSA对成瘾相关行为的保护特性是否也适用于巧克力味饮料（CFB）这类美味食物。为此，最初训练大鼠在固定比率（FR）10强化程序下通过按压杠杆获取CFB（5%（w/v）雀巢奶粉水溶液）。一旦杠杆反应达到稳定水平，大鼠在四个独立实验中分别接受两种不同剂量范围的SSA（0、0.25、0.5和1mg/kg；0、1、2.5和5mg/kg；腹腔注射）急性处理，并暴露于FR10和累进比率（PR）强化程序。还评估了急性给予SSA（0、0.25、0.5和1mg/kg；腹腔注射）对CFB线索诱导的觅药行为恢复的影响。在FR和PR强化程序下，SSA处理减少了大鼠对CFB的杠杆反应、CFB的自我给药量以及CFB的断点。用5mg/kg SSA处理后，所有变量几乎完全被抑制。SSA处理也抑制了CFB觅药行为的恢复。在自我给药实验后立即让所有大鼠进行倒屏试验，评估发现没有剂量的SSA改变大鼠的运动表现。这些结果表明，急性给予SSA可有效抑制由高度享乐性营养驱动的几种成瘾样行为。这些数据将SSA最近在自我给药酒精、吗啡和可卡因的大鼠中所揭示的抗成瘾特性扩展到了一种极具奖励性的自然刺激物上。
