Phenytoin blocks the reversal of a classically conditioned discriminative eyeblink response in rabbits.
Phenytoin blocks the reversal of a classically conditioned discriminative eyeblink response in rabbits.
复制标题
苯妥英可阻止兔子经典条件性眨眼反应的逆转。
DOI：
10.1111/j.1528-1157.1998.tb01425.x
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发表时间：
1998
期刊：
影响因子：
5.6
通讯作者：
Garraghty,PE
中科院分区：
文献类型：
--
作者：
Churchill,JD;Voss,SE;Miller,DP;Steinmetz,JE;Garraghty,PE
目的：已有报道与苯妥英（PHT）长期治疗相关的认知缺陷。 PHT 可以阻断大鼠从有信号的食欲压杆反应到主动回避反应的转变。我们研究了 PHT 和前药磷苯妥英对兔子的影响，这些兔子需要学习辨别和逆转经典的眨眼条件反射范式。方法：在开始药物治疗之前，训练兔子产生辨别的眨眼反应。集中给予 PHT（n = 7）或全身给予前药磷苯妥英（n = 2）。对照动物同样接受生理盐水（n = 3）或不接受药物治疗（n = 13）集中治疗。然后，兔子在维持各自药物的同时接受刺激逆转挑战。结果：在逆转训练的第一天，对照动物通常对两种音调都表现出较高的反应率，随后几天对新的条件刺激（CS-）的反应性降低。相比之下，经过 PHT 治疗的动物未能抑制对新 CS- 的反应。结论：观察到的反应模式与海马消融兔子中观察到的反应模式相似，这使我们认为苯妥英的不良反应可能是由于海马体的作用所致。
Purpose:Cognitive deficits associated with chronic treatment with phenytoin (PHT) have been reported. PHT blocks transfer from a signaled appetitive bar press to an active avoidance response in rats. We investigated the effects of PHT and the prodrug fosphenytoin in rabbits required to learn a discrimination and reversal of a classical eyeblink conditioning paradigm.Methods:Before drug treatment was started, rabbits were trained to produce a discriminated eyeblink response. PHT (n = 7) was administered centrally or the prodrug fosphenytoin (n = 2) was given systemically. Control animals were similarly treated centrally with either saline (n = 3) or no drug treatment (n = 13). Rabbits were then challenged with a stimulus reversal while being maintained on the respective drug.Results:On the first day of reversal training, control animals typically displayed high response rates to both tones, followed by a reduction in responsiveness to the new conditioned stimulus (CS‐) in the ensuing days. In contrast, PHT‐treated animals failed to suppress responsiveness to the new CS‐.Conclusions:The response patterns observed are similar to those observed in rabbits with hippocampal ablations, leading us to suggest that the adverse effects of phenytoin may be due to actions in the hippocampus.