Hlinak Zdenek, Krejci Ivan, Hynie Sixtus, Klenerova Vera
Laboratory of Biochemical Neuropharmacology, Institute of Medical Biochemistry, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
Neuro Endocrinol Lett. 2008 Dec;29(6):917-23.
On the animal model of trimethyltin (TMT) induced behavioral deficits the effect of chronic treatment with spirocyclic dipeptide cyclo/alanyl-l-amino-l-cyclopentane-carbonyl (alaptide, AL) was evaluated in adult male rats.
Changes in the spontaneous behavioral repertoire were investigated in the open-field test on Day 21 (Session 1) and Day 28 (Session 2) after a single oral TMT administration.
In Experiment 1, rats given the highest TMT dose (7.5 mg/kg) exhibited significantly increased total number of behavioral patterns, the floor sniffing being the most frequent pattern. While the medium TMT dose (5 mg/kg) had a similar effect only in Session 1, the lowest TMT dose (2.5 mg/kg) was entirely ineffective. In Experiment 2, an explicit beneficial influence of both AL doses (5 and 10 mg/kg) given for 10 days before and 10 days after TMT (7.5 mg/kg) on the spontaneous behavior repertoire was observed in both Session 1 and Session 2. The total number of patterns and the time spent in individual patterns of AL+TMT treated animals did not differ from the controls and those given AL alone.
We conclude that sufficiently long AL treatment interfered with deleterious effects of TMT and forestalled changes in the structure and timing of spontaneous behavioral patterns. Thus, AL can be designated as a substance having "neuroprotective" effects.
在三甲基锡(TMT)诱导行为缺陷的动物模型上,评估成年雄性大鼠长期使用螺环二肽环/丙氨酰-L-氨基-L-环戊烷羰基(alaptide,AL)治疗的效果。
在单次口服TMT后的第21天(第1阶段)和第28天(第2阶段)进行旷场试验,研究自发行为表现的变化。
在实验1中,给予最高TMT剂量(7.5mg/kg)的大鼠行为模式总数显著增加,其中嗅地是最频繁的模式。中等TMT剂量(5mg/kg)仅在第1阶段有类似效果,而最低TMT剂量(2.5mg/kg)则完全无效。在实验2中,在TMT(7.5mg/kg)给药前10天和给药后10天给予两种AL剂量(5和10mg/kg),在第1阶段和第2阶段均观察到对自发行为表现有明显的有益影响。接受AL+TMT治疗的动物的模式总数和在各个模式中花费的时间与对照组和单独给予AL的动物没有差异。
我们得出结论,足够长时间的AL治疗可干扰TMT的有害影响,并防止自发行为模式的结构和时间发生变化。因此,AL可被指定为具有“神经保护”作用的物质。