Becker Axel, Grecksch Gisela
Faculty of Medicine, Institute of Pharmacology and Toxicology, Otto-von-Guericke University, Leipziger Str 44, 39120 Magdeburg, Germany.
Pharmacol Biochem Behav. 2003 Aug;76(1):1-8. doi: 10.1016/s0091-3057(03)00139-4.
Neonatal ibotenic acid lesion of the ventral hippocampus results in altered patterns of social behaviour. After puberty, lesioned animals spent less time in social interaction and the nonaggressive/aggressive behaviour ratio shifted towards increased aggressiveness. In this study, the effects on social behaviour of the neuroleptic drugs haloperidol (HAL) and clozapine (CLO) after acute and subchronic treatment were studied. Seven-day-old rats were lesioned and social behaviour was tested at the age of 13 weeks. Drug effects were tested after acute (HAL 0.025 mg/kg, CLO 1.0 mg/kg) and subchronic (10 injections, HAL 0.075 mg/kg, CLO 5.0 mg/kg) administration. For comparison, diazepam (DZP, 0.5 mg/kg) was used in the acute experiment. After acute administration, DZP had no effect on social behaviour in sham-lesioned rats, but nonaggressive behaviour increased significantly in lesioned animals. CLO and HAL did reduce the time sham-lesioned rats spent in social contact, and CLO also increased % nonaggressive behaviour in lesioned rats. Here, HAL had no effect. Subchronic administration did not alter social behaviour in sham-lesioned animals. However, CLO increased the time lesioned animals spent in social interaction, whereas HAL had an effect on nonaggressive behaviour. The results of this study indicate that the lesion model is sensitive to differentiated effects of classical neuroleptic drugs such as HAL and atypical neuroleptic drugs like CLO. It might be a useful tool in the search for potential neuroleptic drugs.
新生大鼠腹侧海马注射鹅膏蕈氨酸会导致社交行为模式改变。青春期后，受损动物在社交互动中花费的时间减少，非攻击性/攻击性的行为比例向攻击性增加的方向转变。在本研究中，研究了抗精神病药物氟哌啶醇（HAL）和氯氮平（CLO）在急性和亚慢性治疗后对社交行为的影响。对7日龄大鼠进行损伤，并在13周龄时测试其社交行为。在急性（HAL 0.025mg/kg，CLO 1.0mg/kg）和亚慢性（注射10次，HAL 0.075mg/kg，CLO 5.0mg/kg）给药后测试药物效果。为作比较，在急性实验中使用了地西泮（DZP，0.5mg/kg）。急性给药后，DZP对假损伤大鼠的社交行为没有影响，但在受损动物中非攻击性行为显著增加。CLO和HAL确实减少了假损伤大鼠在社交接触中花费的时间，并且CLO还增加了受损大鼠的非攻击性行为百分比。在此，HAL没有效果。亚慢性给药并未改变假损伤动物的社交行为。然而，CLO增加了受损动物在社交互动中花费的时间，而HAL对非攻击性行为有影响。本研究结果表明，该损伤模型对HAL等经典抗精神病药物和CLO等非典型抗精神病药物的不同作用敏感。它可能是寻找潜在抗精神病药物的有用工具。
