Ho M Y, Velazquez Martinez D N, Lopez Cabrera M, al-Zahrani S S, Bradshaw C M, Szabadi E
Department of Psychiatry, University of Nottingham, Queen's Medical Centre, UK.
Psychopharmacology (Berl). 1995 Apr;118(3):332-7. doi: 10.1007/BF02245963.
This experiment examined the effect of destroying central noradrenergic neurones, using the selective neurotoxin DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine) on the acquisition and performance of discrimination between two time intervals. Rats that had received systemic treatment with DSP4 and vehicle-treated control rats were trained in a series of discrete trials to press lever A following a 2-s presentation of a light stimulus and lever B following an 8-s presentation of the same stimulus. Both groups acquired the discrimination (> 90% correct choices) within 15 sessions; however, the DSP4-treated group showed significantly slower acquisition than the control group. When stable performance had been attained, 'probe' trials were introduced in which the light was presented for intermediate durations. Both groups showed sigmoid functions relating percent choice of lever B to log stimulus duration. Neither the bisection point (duration corresponding to 50% choice of lever B) nor the Weber fraction differed significantly between the DSP4-treated and control groups. The levels of noradrenaline were markedly reduced in the neocortex and hippocampus of the DSP4-treated group, but the levels of dopamine and 5-hydroxytryptamine were not altered. The results indicate that noradrenaline depletion induced by DSP4 retarded the acquisition of temporal discrimination, but did not impair steady-state discriminative precision.
本实验使用选择性神经毒素DSP4(N-(2-氯乙基)-N-乙基-2-溴苄胺)来破坏中枢去甲肾上腺素能神经元,研究其对两个时间间隔辨别学习和表现的影响。给接受DSP4全身治疗的大鼠以及接受赋形剂治疗的对照大鼠进行一系列离散试验训练,在呈现2秒的光刺激后按压杠杆A,在呈现8秒的相同刺激后按压杠杆B。两组均在15个训练单元内学会了辨别(正确选择率>90%);然而,DSP4治疗组的学习速度明显慢于对照组。当达到稳定表现后,引入“探测”试验,即呈现中间时长的光刺激。两组均呈现出杠杆B的选择百分比与对数刺激时长之间的S形函数关系。DSP4治疗组和对照组之间的平分点(对应杠杆B选择率为50%的时长)和韦伯分数均无显著差异。DSP4治疗组的新皮层和海马体中的去甲肾上腺素水平显著降低,但多巴胺和5-羟色胺水平未改变。结果表明,DSP4诱导的去甲肾上腺素耗竭延缓了时间辨别学习,但并未损害稳态辨别精度。