Mannucci C, Pieratti A, Firenzuoli F, Caputi A P, Calapai G
Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, School of Medicine, University of Messina, Via Consolare Valeria, Policlinico Universitario, 98125 Messina, Italy.
Phytomedicine. 2007 Oct;14(10):645-51. doi: 10.1016/j.phymed.2007.06.005. Epub 2007 Aug 6.
Antidepressants may be effective treatment for smoking cessation and new evidence on relationship between smoking and depression is emerging. Extracts of the plant Hypericum perforatum possess antidepressant activity in humans and reduce nicotine withdrawal signs in mice. Both nicotine and H. perforatum administration elicit changes in serotonin (5-HT) formation in the brain. On this basis, we investigated the possible involvement of 5-HT in the beneficial effects of H. perforatum on nicotine withdrawal signs. With the aim to induce nicotine dependence, nicotine (2 mg/kg, four intraperitoneal injections daily) was administered for 14 days to mice (NM). Saline (controls, M) or H. perforatum extract (Ph 50, 500 mg/kg) were orally administered immediately after the last nicotine injection for 30 days after nicotine withdrawal. Another group of animals treated with nicotine (14 days) and successively with H. perforatum extract was intraperitoneally co-administered with selective 5-HT receptorial antagonist WAY 100635 (WAY) (1 mg/kg). All animals were evaluated for locomotor activity and abstinence signs, 24 after nicotine withdrawal. Brain 5-HT metabolism was evaluated in the cortex of mice sacrificed 30 days after nicotine withdrawal through evaluation of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) and 5-HIAA/5-HT ratio. After nicotine withdrawal measurement of 5-HT metabolism in the cortex showed a reduction of 5-HT content while animals treated only with Hypericum extract showed a significant reduction of total abstinence score compared to controls. WAY inhibited the reduction of total abstinence score induced by H. perforatum. Moreover, 5-HT1A expression has been evaluated 30 days after nicotine withdrawal. Our results, show a significant increase of cortical 5-HT content in NM treated with H. perforatum, with a concomitant significant increase of 5-HT1A receptor. So, it is possible to suggest an involvement of 5-HT in beneficial effects of H. perforatum on suffering produced by nicotine withdrawal in dependent mice.
抗抑郁药可能是戒烟的有效治疗方法，吸烟与抑郁之间关系的新证据正在不断涌现。贯叶连翘植物提取物对人体具有抗抑郁活性，并能减轻小鼠的尼古丁戒断症状。尼古丁和贯叶连翘给药均会引起大脑中血清素（5-羟色胺，5-HT）生成的变化。在此基础上，我们研究了5-羟色胺在贯叶连翘对尼古丁戒断症状的有益作用中可能的参与情况。为诱导尼古丁依赖，对小鼠（NM）连续14天每天腹腔注射尼古丁（2毫克/千克）。在最后一次尼古丁注射后立即口服生理盐水（对照组，M）或贯叶连翘提取物（Ph 50，500毫克/千克），持续30天。另一组先接受尼古丁治疗（14天），随后接受贯叶连翘提取物治疗的动物腹腔注射选择性5-羟色胺受体拮抗剂WAY 100635（WAY）（1毫克/千克）。在尼古丁戒断24小时后，对所有动物的运动活动和戒断症状进行评估。通过评估5-羟色胺、5-羟基吲哚乙酸（5-HIAA）和5-HIAA/5-羟色胺比值，对尼古丁戒断30天后处死的小鼠大脑皮质中的5-羟色胺代谢进行评估。尼古丁戒断后，皮质中5-羟色胺代谢的测量显示5-羟色胺含量降低，而仅接受贯叶连翘提取物治疗的动物与对照组相比，总戒断评分显著降低。WAY抑制了贯叶连翘诱导的总戒断评分降低。此外，在尼古丁戒断30天后评估了5-羟色胺1A受体的表达。我们的结果显示，接受贯叶连翘治疗的小鼠皮质中5-羟色胺含量显著增加，同时5-羟色胺1A受体也显著增加。因此，可以认为5-羟色胺参与了贯叶连翘对尼古丁依赖小鼠尼古丁戒断所产生痛苦的有益作用。
