Wu W R, Zhu X Z
Department of Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences.
Eur J Pharmacol. 1999 Jan 1;364(1):1-6. doi: 10.1016/s0014-2999(98)00831-0.
The present study investigated the reinforcing effect of L-deprenyl on conditioned place preference in mice and its mechanism. Conditioned place preference was induced by 10 and 25 mg/kg L-deprenyl in a dose-dependent fashion during five consecutive conditioning days, and its reinforcing property was about five-fold less potent than that of L-amphetamine. Pretreatment with the dopamine antagonist, haloperidol (1 mg/kg i.p.), effectively blocked the place preference produced by L-deprenyl (10 and 25 mg/kg i.p.) and L-amphetamine (2 and 5 mg/kg i.p.), but haloperidol itself produced no place aversion. The neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 30 mg/kg did not modify the place preference induced by both L-deprenyl and L-amphetamine, though the dopamine concentration in striata assayed by high performance liquid chromatography with electrochemical detection (HPLC-EC) was significantly reduced. These results suggest that L-deprenyl has amphetamine-like reinforcing properties. The reinforcing effect of L-deprenyl may be mediated by central dopaminergic neuronal systems, while the nigrostriatal dopaminergic pathway is not involved.
本研究调查了L-司来吉兰对小鼠条件性位置偏爱及其机制的强化作用。在连续五个条件反射日期间，10和25mg/kg的L-司来吉兰以剂量依赖性方式诱导条件性位置偏爱，其强化特性的效力约为L-苯丙胺的五分之一。用多巴胺拮抗剂氟哌啶醇（1mg/kg腹腔注射）预处理可有效阻断L-司来吉兰（10和25mg/kg腹腔注射）和L-苯丙胺（2和5mg/kg腹腔注射）产生的位置偏爱，但氟哌啶醇本身不会产生位置厌恶。神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP），30mg/kg，虽然通过高效液相色谱电化学检测（HPLC-EC）测定的纹状体中多巴胺浓度显著降低，但并未改变L-司来吉兰和L-苯丙胺诱导的位置偏爱。这些结果表明，L-司来吉兰具有类似苯丙胺的强化特性。L-司来吉兰的强化作用可能由中枢多巴胺能神经元系统介导，而黑质纹状体多巴胺能通路不参与其中。
