Long-term haloperidol administration enhances and short-term administration attenuates the behavioral effects of cocaine in a place conditioning procedure.
Long-term haloperidol administration enhances and short-term administration attenuates the behavioral effects of cocaine in a place conditioning procedure.
复制标题
长期施用氟哌啶醇可增强而短期施用可减弱可卡因在场所调理过程中的行为影响。
DOI：
10.1007/s002130050138
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发表时间：
1996
影响因子：
3.4
通讯作者：
Nestler,EJ
中科院分区：
文献类型：
--
作者：
Kosten,TA;DeCaprio,JL;Nestler,EJ
可卡因的许多行为效应可被多巴胺（DA）受体拮抗剂减弱。然而，长期DA拮抗剂给药可以增强包括中边缘系统在内的几种途径中神经元对DA的反应性。本研究比较了短期与长期给予多巴胺拮抗剂氟哌啶醇对可卡因位置条件反射的影响。在短期研究中，将大鼠维持在氟哌啶醇或溶剂中10天的位置调节。中等剂量可卡因（10-15 mg/kg）的位置条件反射显著减弱，与氟哌啶醇和可卡因的多巴胺能作用一致。在第二项研究中，大鼠在位置条件反射后给予氟哌啶醇，这对这种行为的表达没有影响。最后，在位置调节和测试之前和整个过程中，大鼠维持氟哌啶醇30天，这导致低可卡因剂量（2.5-7.5 mg/kg）下的显著位置调节。由于这些可卡因剂量不支持在车辆维持大鼠的位置条件反射，这些数据表明，长期氟哌啶醇管理增强这些行为效应的敏感性与短期氟哌啶醇管理所见的衰减。这些结果对可卡因滥用治疗具有广泛的影响，特别是在精神分裂症人群中。
Many behavioral effects of cocaine are attenuated by dopamine (DA) receptor antagonists. Yet, long-term DA antagonist administration enhances neuronal responsiveness to DA in several pathways, including the mesolimbic system. This study compared the effects of short-term versus long-term administration of the DA antagonist, haloperidol, on cocaine place conditioning. In the short-term study, rats were maintained on haloperidol or vehicle for the 10 days of place conditioning. Place conditioning to moderate doses of cocaine (10–15 mg/kg) was attenuated significantly, consistent with the dopaminergic actions of haloperidol and cocaine. In the second study, rats were administered haloperidol after place conditioning which had no effect on the expression of this behavior. Finally, rats were maintained on haloperidol for 30 days prior to and throughout place conditioning and testing which resulted in significant place conditioning at low cocaine doses (2.5–7.5 mg/kg). Because these cocaine doses do not support place conditioning in vehicle-maintained rats, these data suggest that long-term haloperidol administration enhances the sensitivity to these behavioral effects in contrast to the attenuation seen with short-term haloperidol administration. These results have wide-ranging implications for cocaine abuse treatment, particularly among schizophrenic populations.