Rocha B A, Ator R, Emmett-Oglesby M W, Hen R
Department of Pharmacology, University of North Texas Health Science Center, Fort Worth 76107, USA.
Pharmacol Biochem Behav. 1997 Jul;57(3):407-12. doi: 10.1016/s0091-3057(96)00444-3.
The present experiment tested the hypothesis that 5-HT1B receptors are involved in the reinforcing effects of cocaine. Transgenic mice lacking 5-HT1B receptors were used as subjects and compared with wild-type mice for the acquisition and maintenance of intravenous (IV) cocaine self-administration. Male 129/Sv-ter and 5-HT1B-minus 129/Sv-ter inbred mice (Columbia University, New York) were initially trained to press a lever under a fixed-ratio schedule 2, first for sweetened condensed milk as reinforcer and subsequently for cocaine (2.0 mg/kg/infusion). When a stable baseline of responding was obtained, each subject was tested under different doses of cocaine (1.0, 2.0, and 4.0 mg/kg), with the number of reinforcers per hour used as the dependent variable. Both strains successfully acquired food-shaping and cocaine self-administration, but the mutant mice presented a significantly shorter latency to meet IV cocaine self-administration acquisition criteria (p < 0.05). However, both wild-type and mutant mice had similar dose-response to cocaine. These results suggest that the 5-HT1B receptors may be implicated in the propensity to self-administer cocaine, but other mechanisms might be involved in the maintenance of cocaine self-administration.
本实验检验了5-羟色胺1B（5-HT1B）受体参与可卡因强化作用的假设。将缺乏5-HT1B受体的转基因小鼠作为实验对象，并与野生型小鼠比较静脉注射可卡因自我给药的习得和维持情况。雄性129/Sv-ter和5-HT1B基因敲除的129/Sv-ter近交系小鼠（纽约哥伦比亚大学）最初接受固定比率为2的杠杆按压训练，首先以甜炼乳作为强化物，随后以可卡因（2.0毫克/千克/注射）作为强化物。当获得稳定的反应基线后，对每只实验对象进行不同剂量可卡因（1.0、2.0和4.0毫克/千克）测试，每小时强化物数量作为因变量。两个品系均成功习得食物塑造和可卡因自我给药，但突变小鼠达到静脉注射可卡因自我给药习得标准的潜伏期显著缩短（p<0.05）。然而，野生型和突变型小鼠对可卡因的剂量反应相似。这些结果表明，5-HT1B受体可能与可卡因自我给药倾向有关，但其他机制可能参与可卡因自我给药的维持。
