Svingos A L, Hitzemann R
State University of New York, Department of Psychiatry, Stony Brook 11794-8101.
Pharmacol Biochem Behav. 1992 Nov;43(3):871-9. doi: 10.1016/0091-3057(92)90420-k.
We report results in rats pretreated with (+/-)-zacopride (0.03 mg/kg, IP), ICS 205-930 (0.1 mg/kg, IP), and MDL 72222 (1.0 mg/kg, IP) 15 min before challenge with (-)-cocaine (10.0 mg/kg, IP). At a dose of 10 micrograms/kg, zacopride significantly inhibited (approximately 50%) cocaine-induced locomotion. We also investigated whether or not 5-hydroxytryptamine3 (5-HT3) antagonists block the cocaine binding site on the dopamine transporter and/or affect the ability of dopamine to regulate this binding site. In well-washed striatal membranes, neither zacopride nor ICS 205-930 (10(-9)-10(-5) M) inhibited [3H]2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane ([3H]WIN 35,428) (0.3 nM) binding. Furthermore, neither of these compounds affected the ability of dopamine to block WIN 35,428 binding. To determine if 5-HT is required for the 5-HT3 antagonist effect, we examined the interaction between cocaine and zacopride in rats pretreated with p-chlorophenylalanine (PCPA) (3 days x 100 mg/kg/day). PCPA pretreatment shifted the cocaine dose-response curve to the right and blocked the ability of zacopride to reverse cocaine-induced activity.
我们报告了在用（±）-扎考必利（0.03mg/kg，腹腔注射）、ICS 205-930（0.1mg/kg，腹腔注射）和MDL 72222（1.0mg/kg，腹腔注射）预处理15分钟后，用（-）-可卡因（10.0mg/kg，腹腔注射）进行激发的大鼠实验结果。在剂量为10微克/千克时，扎考必利显著抑制（约50%）可卡因诱导的运动。我们还研究了5-羟色胺3（5-HT3）拮抗剂是否阻断多巴胺转运体上的可卡因结合位点和/或影响多巴胺调节该结合位点的能力。在充分洗涤的纹状体膜中，扎考必利和ICS 205-930（10⁻⁹ - 10⁻⁵ M）均未抑制[³H]2β-甲氧基羰基-3β-（4-氟苯基）托烷（[³H]WIN 35,428）（0.3 nM）的结合。此外，这些化合物均未影响多巴胺阻断WIN 35,428结合的能力。为了确定5-HT是否是5-HT3拮抗剂作用所必需的，我们检查了用对氯苯丙氨酸（PCPA）（3天×100mg/kg/天）预处理的大鼠中可卡因和扎考必利之间的相互作用。PCPA预处理使可卡因剂量-反应曲线右移，并阻断了扎考必利逆转可卡因诱导活性的能力。
