Šlamberová R, Nohejlová K, Ochozková A, Mihalčíková L
Department of Physiology, Third Faculty of Medicine, Charles University, Praha 2, Czech Republic.
Physiol Res. 2018 Dec 31;67(Suppl 4):S665-S672. doi: 10.33549/physiolres.934053.
Psychostimulants, as well as cannabinoids, have been shown to significantly affect a great variety of behaviors in both humans and laboratory animals. Our previous studies have repeatedly demonstrated that the application of the vehicle for psychostimulants, i.e. saline, to control groups, generated different behavioral test results compared to absolute naive controls (i.e. without any injection). Therefore, our present study has set three goals: (1) to evaluate the effect of three different psychostimulant drugs, (2) to evaluate the effect of three doses of delta 9-tetrahydrocannabinol (THC), and (3) to evaluate the effect of saline and ethanol injections vs sham injections and no injection on spontaneous behavior of adult male rats. The LABORAS test (Metris B.V., Netherlands) was used to examine spontaneous locomotor activity and exploratory behavior in an unknown environment over 1 h. In Experiment 1, psychostimulant drugs were tested: single subcutaneous (s.c.) injections of amphetamine (5 mg/kg), cocaine (5 mg/kg), and 3,4-methylenedioxymethamphetamine (MDMA) (5 mg/kg) were applied prior to testing. Control animals received the same volume (1 ml/kg) of s.c. saline. In Experiment 2, the effect of three doses of THC (1, 2, and 5 mg/kg, s.c.) were examined. An s.c. injection of vehicle (ethanol) was used as a control. In Experiment 3, injections of saline and ethanol were compared to the group receiving a sham s.c. injection and to a group of absolute "naive" controls. Our results demonstrated that (1) all psychostimulants increased locomotion time, distance traveled, and speed while decreasing immobility time of adult male rats relative to saline controls. The most prominent effect was associated with MDMA; (2) The effect of THC was dose-dependent and was most apparent within the first 10 min of the LABORAS test. (3) With regard to the effect of injection: absolute controls (without injection) compared to animals injected with ethanol, saline, or sham-injected displayed reduced immobility time, traveled longer distances, and had increased speed. In conclusion, our data showed drug dependent behavioral changes in adult male rats after application of psychostimulants and cannabinoids. Our findings also suggest that not only drugs but the actual single injection per se also affects the behavior of laboratory animals in an unknown environment. This effect seems to be associated with the acute stress associated with the injection.
精神兴奋剂以及大麻素已被证明会显著影响人类和实验动物的多种行为。我们之前的研究反复表明，给对照组注射精神兴奋剂的溶媒即生理盐水，与绝对未处理的对照组（即未进行任何注射）相比，会产生不同的行为测试结果。因此，我们目前的研究设定了三个目标：（1）评估三种不同精神兴奋剂药物的效果；（2）评估三种剂量的δ9 - 四氢大麻酚（THC）的效果；（3）评估生理盐水和乙醇注射与假注射及不注射相比，对成年雄性大鼠自发行为的影响。使用LABORAS测试（荷兰Metris B.V.公司）在1小时内检测未知环境中的自发运动活动和探索行为。在实验1中，测试精神兴奋剂药物：在测试前单次皮下注射苯丙胺（5毫克/千克）、可卡因（5毫克/千克）和3,4 - 亚甲基二氧甲基苯丙胺（摇头丸，MDMA）（5毫克/千克）。对照动物接受相同体积（1毫升/千克）的皮下生理盐水注射。在实验2中，检测三种剂量的THC（1、2和5毫克/千克，皮下注射）的效果。皮下注射溶媒（乙醇）作为对照。在实验3中，将生理盐水和乙醇注射组与接受假皮下注射的组以及绝对“未处理”对照组进行比较。我们的结果表明：（1）与生理盐水对照组相比，所有精神兴奋剂均增加了成年雄性大鼠的运动时间、行进距离和速度，同时减少了静止时间。最显著的效果与摇头丸相关；（2）THC的效果呈剂量依赖性，且在LABORAS测试的前10分钟内最为明显；（3）关于注射的影响：与注射乙醇、生理盐水或接受假注射的动物相比，绝对对照组（未注射）的静止时间减少，行进距离更长，速度增加。总之，我们的数据显示在应用精神兴奋剂和大麻素后成年雄性大鼠出现了药物依赖性行为变化。我们的研究结果还表明，不仅药物本身，实际的单次注射本身也会影响实验动物在未知环境中的行为。这种影响似乎与注射相关的急性应激有关。
