Minnema D J, Hendry J S, Rosecrans J A
Psychopharmacology (Berl). 1984;83(2):200-4. doi: 10.1007/BF00429735.
Rats were trained to discriminate the putative serotonin (5-HT) antagonist, pizotifen maleate (BC105), from saline using a two-lever drug discrimination paradigm. Pizotifen maleate (6 mg/kg, 14.6 mumol/kg, IP) or saline was administered 55 min prior to the operant training session. The pizotifen discriminative stimulus (DS) had a rapid onset (less than 7 min) and was of long duration. The pizotifen DS was dose dependent. The pizotifen DS did not generalize to the putative 5-HT antagonists, methiothepin, xylamidine, and cinanserin. Partial generalization was observed to methysergide and metergoline, and complete generalization to cyrproheptadine and the phenothiazine antihistamine, promethazine. The pizotifen DS failed to generalize to the antipsychotic chlorpromazine, the ethanolamine antihistamine diphenhydramine, the CNS stimulant, d-amphetamine, and the putative 5-HT agonists, LSD and quipazine. LSD and quipazine failed to antagonize the pizotifen DS. The results of this study suggest that different DS properties are associated with the different putative 5-HT antagonists and that pizotifen and cyproheptadine, in addition to their reported 5-HT antagonist properties, share a common property that is also associated with promethazine, probably involving antihistaminergic activity.
使用双杠杆药物辨别范式训练大鼠，使其能够区分假定的血清素（5-羟色胺，5-HT）拮抗剂马来酸匹唑替芬（BC105）和生理盐水。在操作性训练前55分钟，腹腔注射马来酸匹唑替芬（6毫克/千克，14.6微摩尔/千克）或生理盐水。马来酸匹唑替芬的辨别刺激（DS）起效迅速（不到7分钟）且持续时间长。该辨别刺激呈剂量依赖性。马来酸匹唑替芬的辨别刺激不会泛化到假定的5-HT拮抗剂甲硫噻嗪、赛拉米定和辛那色林。观察到对甲基麦角新碱和麦角苄酯有部分泛化，对赛庚啶和吩噻嗪类抗组胺药异丙嗪有完全泛化。马来酸匹唑替芬的辨别刺激未能泛化到抗精神病药物氯丙嗪、乙醇胺类抗组胺药苯海拉明、中枢神经系统兴奋剂d-苯丙胺以及假定的5-HT激动剂麦角酸二乙胺（LSD）和喹哌嗪。LSD和喹哌嗪未能拮抗马来酸匹唑替芬的辨别刺激。本研究结果表明，不同的辨别刺激特性与不同的假定5-HT拮抗剂相关，并且马来酸匹唑替芬和赛庚啶除了已报道的5-HT拮抗剂特性外，还具有一种与异丙嗪共有的特性，可能涉及抗组胺活性。
