Perfumi Marina, Mattioli Laura, Cucculelli Marino, Massi Maurizio
Department of Pharmacological Sciences and Experimental Medicine, University of Camerino, 62032 Camerino, Italy.
J Psychopharmacol. 2005 Sep;19(5):448-54. doi: 10.1177/0269881105056519.
Acute treatment with extracts of Hypericum perforatum, the common plant usually called St. John's Wort, reduces voluntary ethanol intake in Marchigian Sardinian alcohol-preferring (msP) rats and acts synergistically with opioid receptor antagonists to further attenuate ethanol consumption. The present study evaluated the effect of chronic (once a day for 12 days) intragastric administration of a CO2 Hypericum perforatum extract (HPCO2), given alone or combined with naltrexone (NTX), on ethanol intake offered 2h/day in msP rats. Chronic treatment with HPCO2 markedly reduced ethanol intake at the dose of 125, but not at 7 mg/kg; the effect of 125 mg/kg was observed since the first day of treatment and remained constant across the 12 days. The same dose of HPCO2 slightly reduced the simultaneous intake of food only on day 3 and day 11 of treatment. Treated rats promptly recovered baseline ethanol intake when treatment did not precede access to ethanol (on day 8) or after the end of treatment (day 13 and day 14), suggesting that HPCO2 administrations did not induce conditioned aversion to alcohol. Chronic intraperitoneal treatment with NTX reduced ethanol intake at 3, but not at 0.5mg/kg. The synergistic effect on ethanol intake of HPCO2 and NTX was evident also in conditions of chronic treatment. HPCO2, 7 mg/kg, and NTX, 0.5mg/kg, evoked a pronounced and statistically significant reduction of ethanol intake, while being inactive. The effect on ethanol intake of the combined treatment remained stable over the 12 days of treatment; food intake was slightly reduced only on day 3 and on day 7 in response to 125 mg/kg of HPCO2 combined with NTX 0.5mg/kg, but no difference in body weight between controls and treated rats was observed at the end of treatment. Following 12-day treatment with 125 mg/kg of HPCO2, no difference was observed in the responsivity of msP rats to the effect on ethanol intake of several doses of the extract. In conclusion, the present results provide evidence for a selective and pronounced effect of HPCO2, alone or combined with naltrexone, on ethanol intake in conditions of chronic treatment, without development of tolerance. These findings further support the view that clinical trials for extracts of Hypericum perforatum in the treatment of alcoholism should be considered.
贯叶连翘（一种通常被称为圣约翰草的常见植物）提取物的急性治疗可降低马尔凯-撒丁岛嗜酒（msP）大鼠的自愿乙醇摄入量，并与阿片受体拮抗剂协同作用，进一步减少乙醇消耗。本研究评估了慢性（每天一次，共12天）胃内给予二氧化碳超临界萃取的贯叶连翘提取物（HPCO2）单独使用或与纳曲酮（NTX）联合使用，对msP大鼠每天2小时提供的乙醇摄入量的影响。用HPCO2进行慢性治疗，剂量为125mg/kg时可显著降低乙醇摄入量，但7mg/kg时则无此效果；从治疗第一天起就观察到125mg/kg的效果，并且在12天内保持不变。相同剂量的HPCO2仅在治疗的第3天和第11天略微减少了同时的食物摄入量。当治疗不在获取乙醇之前进行（第8天）或在治疗结束后（第13天和第14天），接受治疗的大鼠迅速恢复到基线乙醇摄入量，这表明给予HPCO2并未诱导对酒精的条件性厌恶。用NTX进行慢性腹腔注射治疗，剂量为3mg/kg时可降低乙醇摄入量，但0.5mg/kg时则无此效果。在慢性治疗条件下，HPCO2和NTX对乙醇摄入量的协同作用也很明显。7mg/kg的HPCO2和0.5mg/kg的NTX可引起乙醇摄入量显著且有统计学意义的降低，而单独使用时则无活性。联合治疗对乙醇摄入量的影响在12天的治疗过程中保持稳定；仅在第3天和第7天，当125mg/kg的HPCO2与0.5mg/kg的NTX联合使用时，食物摄入量略有减少，但在治疗结束时，对照组和治疗组大鼠的体重没有差异。用125mg/kg的HPCO2进行12天治疗后，msP大鼠对几种剂量提取物对乙醇摄入量影响的反应性没有差异。总之，本研究结果提供了证据，表明HPCO2单独使用或与纳曲酮联合使用，在慢性治疗条件下对乙醇摄入量有选择性且显著的影响，且不会产生耐受性。这些发现进一步支持了应考虑对贯叶连翘提取物治疗酒精中毒进行临床试验的观点。
