Schechter M D, Meehan S M
Department of Pharmacology, Northeastern Ohio Universities College of Medicine, Rootstown 44272-0095.
Pharmacol Biochem Behav. 1992 Apr;41(4):807-12. doi: 10.1016/0091-3057(92)90231-4.
Rats were trained to discriminate the interoceptive stimuli produced by subcutaneously administered 0.4 mg/kg nicotine in a two-lever, food-motivated, operant task. Once criterion performance was attained, dose-response experiments indicated an ED50 value of 0.1 mg/kg and subsequent time course experiments showed a maximal effect between 10 and 30 min postadministration with a return to saline-like responding at 2 h. Pretreatment with the presynaptic dopamine release inhibitors CGS 10746B (30 mg/kg), as well as with the dihydropyridine calcium blocker isradipine (15 mg/kg), each produced a significant blockade of nicotine discrimination. In contrast, the 5-hydroxytryptamine (5-HT) receptor 5-HT3 antagonist ICS-205930 did not produce any effect upon nicotine discrimination. Thus, drugs that interfere with calcium influx, viz., isradipine, or with dopamine release (CGS 10746B) also interfere with nicotine discrimination and these results suggest that calcium influx and dopamine release may be necessary conditions for nicotine discrimination.
在一项双杠杆、以食物为动机的操作性任务中，训练大鼠辨别皮下注射0.4 mg/kg尼古丁所产生的内感受性刺激。一旦达到标准表现，剂量反应实验表明ED50值为0.1 mg/kg，随后的时程实验显示给药后10至30分钟出现最大效应，2小时后恢复到类似生理盐水的反应。用突触前多巴胺释放抑制剂CGS 10746B（30 mg/kg）以及二氢吡啶类钙阻滞剂伊拉地平（15 mg/kg）进行预处理，均显著阻断了尼古丁辨别。相比之下，5-羟色胺（5-HT）受体5-HT3拮抗剂ICS-205930对尼古丁辨别没有任何影响。因此，干扰钙内流的药物，即伊拉地平，或干扰多巴胺释放的药物（CGS 10746B）也会干扰尼古丁辨别，这些结果表明钙内流和多巴胺释放可能是尼古丁辨别的必要条件。
