Marcel D, Bardelay C, Hunt P F
Neuropharmacology. 1986 Mar;25(3):283-6. doi: 10.1016/0028-3908(86)90253-4.
The effect of lesioning noradrenergic pathways on the benzodiazepine receptor has been studied using a novel neurotoxic agent, N(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) which has better selectivity than the classical 6-hydroxydopamine (6-OHDA) towards noradrenergic neurones, and which has the added advantage of being injected systemically rather than intracerebrally. Three different radioligands were used: an agonist, [3H]flunitrazepam, an antagonist, [3H]Ro 15-1788, and a partial agonist [3H]RU 43028. Binding was measured using membrane homogenates from the cortex and hippocampus of the rat, two regions of the brain which receive an extensive noradrenergic innervation. In contrast to previous reports of a decrease in the binding of [3H]flunitrazepam following lesioning with 6-OHDA, no significant change was observed in either the affinity (KD) or the number of sites (Bmax) of any one of these ligands after lesioning with DSP4. While the reasons for this discrepancy are not clear, these results do not confirm that destruction of noradrenergic afferents to the cortex or hippocampus leads to any modification of the benzodiazepine receptor as demonstrated by ligand binding.
使用一种新型神经毒素N(2-氯乙基)-N-乙基-2-溴苄胺（DSP4）研究了损毁去甲肾上腺素能通路对苯二氮䓬受体的影响。与经典的6-羟基多巴胺（6-OHDA）相比，DSP4对去甲肾上腺素能神经元具有更好的选择性，并且具有可全身注射而非脑内注射的额外优势。使用了三种不同的放射性配体：一种激动剂[3H]氟硝西泮、一种拮抗剂[3H]Ro 15-1788和一种部分激动剂[3H]RU 43028。使用大鼠大脑中接受广泛去甲肾上腺素能神经支配的两个区域——皮质和海马体的膜匀浆来测量结合情况。与先前关于用6-OHDA损毁后[3H]氟硝西泮结合减少的报道相反，在用DSP4损毁后，这些配体中任何一种的亲和力（KD）或位点数量（Bmax）均未观察到显著变化。虽然这种差异的原因尚不清楚，但这些结果并未证实如配体结合所示，向皮质或海马体的去甲肾上腺素能传入纤维的破坏会导致苯二氮䓬受体的任何改变。
