Salamone J D, Cousins M S, Maio C, Champion M, Turski T, Kovach J
Department of Psychology, University of Connecticut, Storrs, 06269-1020, USA.
Psychopharmacology (Berl). 1996 May;125(2):105-12. doi: 10.1007/BF02249408.
Rats were tested using a lever pressing/feeding procedure in which a preferred food (Bioserve pellets) was available by pressing a lever on a fixed ratio 5 schedule, but a less preferred food (lab chow) was also available concurrently in the operant chamber. The effects of repeated (14 day) injections of haloperidol, clozapine and thioridazine were compared. Haloperidol (0.05-0.15 mg/kg) significantly reduced lever pressing and increased chow intake throughout the drug treatment period. Injections of clozapine (2.0-6.0 mg/kg) suppressed lever pressing but failed to produce substantial increases in chow intake. In the haloperidol experiment there was a significant inverse correlation between lever pressing and chow intake, but in the clozapine experiment there was not. Regression analysis indicated that rats treated with the high dose of clozapine showed some tolerance to the suppression of lever pressing. Tests of sedation also were conducted before and after the instrumental behavior sessions. Haloperidol produced little or no sedative effect in the dose range tested. Clozapine produced substantial sedation during the first 10 days of administration, but this effect, like the suppression of lever pressing, showed signs of tolerance. Thioridazine (3.0-9.0 mg/kg) produced some effects that resembled haloperidol, and other effects, including sedation, that resembled clozapine. These studies indicate that haloperidol suppresses lever pressing for food at low doses that do not produce severe motivational or sedative effects that disrupt food intake. In contrast, it appears as though the suppression of lever pressing produced by clozapine stems from a sedative effect that also serves to set limits on chow intake. These results indicate that haloperidol and clozapine suppress lever pressing through different mechanisms.
使用杠杆按压/喂食程序对大鼠进行测试，在此程序中，通过按固定比率5的时间表按压杠杆可获得一种偏好的食物（Bioserve颗粒饲料），但在操作箱中同时也可获得一种不太偏好的食物（实验室用普通饲料）。比较了重复（14天）注射氟哌啶醇、氯氮平和硫利达嗪的效果。在整个药物治疗期间，氟哌啶醇（0.05 - 0.15毫克/千克）显著减少杠杆按压并增加普通饲料摄入量。注射氯氮平（2.0 - 6.0毫克/千克）抑制杠杆按压，但未能使普通饲料摄入量大幅增加。在氟哌啶醇实验中，杠杆按压与普通饲料摄入量之间存在显著的负相关，但在氯氮平实验中则不存在。回归分析表明，用高剂量氯氮平治疗的大鼠对杠杆按压抑制表现出一定的耐受性。在工具性行为实验前后也进行了镇静测试。在测试的剂量范围内，氟哌啶醇几乎没有或没有产生镇静作用。氯氮平在给药的前10天产生了显著的镇静作用，但这种作用与杠杆按压抑制一样，显示出耐受迹象。硫利达嗪（3.0 - 9.0毫克/千克）产生了一些类似于氟哌啶醇的效果，以及其他类似于氯氮平的效果，包括镇静作用。这些研究表明，氟哌啶醇在低剂量时抑制为获取食物而进行的杠杆按压，这些低剂量不会产生严重影响进食动机或导致镇静从而干扰食物摄入的作用。相比之下，氯氮平产生的杠杆按压抑制似乎源于一种镇静作用，这种镇静作用也对普通饲料摄入量起到了限制作用。这些结果表明，氟哌啶醇和氯氮平通过不同机制抑制杠杆按压。
