Stinus L, Nadaud D, Deminière J M, Jauregui J, Hand T T, Le Moal M
INSERM U.259, Université de Bordeaux II, France.
Biol Psychiatry. 1989 Aug;26(4):363-71. doi: 10.1016/0006-3223(89)90052-8.
The behavioral effects of systemic heroin administration were examined in rats subjected to flupentixol impregnation prior to and during behavioral testing. In the first experiment, the dose of heroin required to produce a place preference was determined in two groups of rats, one of which had received chronic flupentixol decanoate (12 mg/kg, sc, every 10 days for 6 weeks) and the other which had received the palm oil vehicle during the same time period. It was found that whereas 60 micrograms/kg of heroin was required to produce a place preference in control rats, only 7.5 micrograms/kg was sufficient to do so in chronic neuroleptic-treated rats. In a second experiment, the locomotor activating effect of heroin was evaluated in two groups of rats that had been subjected to the same chronic regimen as in Experiment 1. Locomotor activity was enhanced in both groups following 120 micrograms/kg heroin, whereas 30 micrograms/kg was ineffective in either group. Finally, it was found that neuroleptic-treated, but not control, rats rapidly learned to self-administer intravenous infusions of an unusually low dose of heroin (4 micrograms) and to discriminate these infusions from vehicle infusions. Together, these data show that chronic dopamine (DA) receptor blockade produces a marked increase in the sensitivity to the reinforcing and discriminative stimulus properties of systemic heroin administration and that this increase is not attributable to heroin-induced locomotor activation. The results are discussed in terms of the role of DA systems in opiate reinforcement processes.
在行为测试之前及测试期间对接受氟哌噻吨注入的大鼠进行了全身性海洛因给药的行为效应研究。在第一个实验中，测定了两组大鼠产生位置偏好所需的海洛因剂量，其中一组大鼠接受了癸酸氟哌噻吨（12毫克/千克，皮下注射，每10天一次，共6周），另一组大鼠在同一时期接受了棕榈油载体。结果发现，对照大鼠产生位置偏好需要60微克/千克的海洛因，而在慢性抗精神病药物治疗的大鼠中，仅7.5微克/千克就足以产生位置偏好。在第二个实验中，对两组接受与实验1相同慢性方案的大鼠评估了海洛因的运动激活作用。两组在注射120微克/千克海洛因后运动活性均增强，而30微克/千克对两组均无效。最后，发现经抗精神病药物治疗的大鼠而非对照大鼠迅速学会自行静脉注射异常低剂量的海洛因（4微克），并将这些注射与载体注射区分开来。这些数据共同表明，慢性多巴胺（DA）受体阻断使对全身性海洛因给药的强化和辨别刺激特性的敏感性显著增加，且这种增加并非归因于海洛因诱导的运动激活。根据DA系统在阿片类强化过程中的作用对结果进行了讨论。
