Body S, Kheramin S, Mobini S, Ho M-Y, Velazquez-Martinez D N, Bradshaw C M, Szabadi E
Psychopharmacology Section, Division of Psychiatry, University of Nottingham, UK.
Behav Pharmacol. 2002 Dec;13(8):603-14. doi: 10.1097/00008877-200212000-00001.
In this experiment we examined the effect of a serotonin receptor (5-HT1A) agonist and antagonist WAY-100635 (N-[2-(4-[2-methoxy-phenyl]-1-piperazinyl)ethyl]-N-2-pyridinylcyclohexane-carboxamide) on temporal differentiation, in intact rats and rats whose serotonergic (5-HTergic) pathways had been destroyed by 5,7-dihydroxytryptamine (5,7-DHT). Thirteen rats received 5,7-DHT-induced lesions of the median and dorsal raphe nuclei; 14 rats received sham lesions. They were trained to press two levers (A and B) in 50-s trials, in which reinforcement was contingent upon responding on A in the first half, and B in the second half, of the trial. Logistic psychophysical curves were fitted to the relative response rate data (percent responding on B, %B), for derivation of timing indices [T50 (time corresponding to %B=50%), slope, Weber fraction] following WAY-100635, 8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetralin], combinations of WAY-100635+8-OH-DPAT, and vehicle alone. WAY-100635 (30, 100 and 300 microg/kg, s.c.) did not affect the timing indices. 8-OH-DPAT (100, 200 microg/kg, s.c.) reduced T50 without affecting the Weber fraction. WAY-100635 (300 microg/kg) abolished the effect of 8-OH-DPAT on T50 in both the lesioned and sham-lesioned groups. 5-HT levels in the neocortex, hippocampus, amygdala, nucleus accumbens and hypothalamus of the lesioned group were <20% of those in the sham-lesioned group; catecholamine levels were unaffected. The results confirm that 8-OH-DPAT disrupts temporal differentiation in a free-operant psychophysical schedule, reducing T50, and indicate that this effect of 8-OH-DPAT is mediated by postsynaptic 5-HT1A receptors.
在本实验中,我们研究了5-羟色胺受体(5-HT1A)激动剂和拮抗剂WAY-100635(N-[2-(4-[2-甲氧基苯基]-1-哌嗪基)乙基]-N-2-吡啶基环己烷甲酰胺)对完整大鼠以及5,7-二羟色胺(5,7-DHT)破坏了其5-羟色胺能(5-HTergic)通路的大鼠时间分辨能力的影响。13只大鼠接受了5,7-DHT诱导的中缝核和背侧中缝核损伤;14只大鼠接受了假损伤。它们接受训练,在50秒的试验中按压两个杠杆(A和B),其中强化取决于在试验的前半段对A的反应以及后半段对B的反应。将逻辑心理物理学曲线拟合到相对反应率数据(对B的反应百分比,%B),以得出WAY-100635、8-OH-DPAT[8-羟基-2-(二正丙基氨基)四氢萘]、WAY-100635+8-OH-DPAT组合以及单独使用溶剂后的时间分辨指数[T50(对应%B = 50%的时间)、斜率、韦伯分数]。WAY-100635(30、100和300微克/千克,皮下注射)不影响时间分辨指数。8-OH-DPAT(100、200微克/千克,皮下注射)降低了T50,但不影响韦伯分数。WAY-100635(300微克/千克)消除了8-OH-DPAT对损伤组和假损伤组T50的影响。损伤组新皮层、海马体、杏仁核、伏隔核和下丘脑的5-羟色胺水平低于假损伤组的20%;儿茶酚胺水平未受影响。结果证实,8-OH-DPAT在自由操作心理物理学程序中破坏时间分辨能力,降低T50,并表明8-OH-DPAT的这种作用是由突触后5-HT1A受体介导的。