Engelbrecht A H, Russell V, Carstens M E, De Villiers A S, Searson A, Jaffer A, Taljaard J J
Department of Chemical Pathology, University of Stellenbosch, Tygerberg Hospital, South Africa.
J Neurosci Methods. 1994 Apr;52(1):57-60. doi: 10.1016/0165-0270(94)90056-6.
In order to determine the specificity of a lesion aimed at the locus coeruleus (LC), various doses of 6-hydroxydopamine (6-OHDA), a neurotoxin which selectively lesions catecholaminergic neurons, were bilaterally infused into the LC. The noradrenaline (NA) concentration in the frontal cortex, hippocampus, hypothalamus, LC, A1 and A2 nuclei decreased with increasing doses of 6-OHDA. A 1 microgram dose of 6-OHDA injected bilaterally into the LC caused maximal depletion of the NA concentration in the frontal cortex, hippocampus and A1 and A2 nuclei. A dose of 2 micrograms 6-OHDA caused further depletion of the NA content of the hypothalamus and LC. These findings suggest that A1 and A2 neurons which project to the hypothalamus may have been lesioned or that the noradrenergic projection from the LC to the hypothalamus may be greater than was previously suspected. Alternatively, leakage of 6-OHDA into the cerebrospinal fluid may have occurred at the higher doses, thus directly exposing the hypothalamus to the toxic effects of 6-OHDA.
为了确定针对蓝斑(LC)的损伤的特异性,将不同剂量的6-羟基多巴胺(6-OHDA,一种选择性损伤儿茶酚胺能神经元的神经毒素)双侧注入LC。随着6-OHDA剂量增加,额叶皮质、海马、下丘脑、LC、A1和A2核中的去甲肾上腺素(NA)浓度降低。双侧向LC注射1微克剂量的6-OHDA导致额叶皮质、海马以及A1和A2核中NA浓度最大程度的耗竭。2微克剂量的6-OHDA导致下丘脑和LC中NA含量进一步耗竭。这些发现表明,投射到下丘脑的A1和A2神经元可能已受损,或者从LC到下丘脑的去甲肾上腺素能投射可能比之前怀疑的更强。另外,在较高剂量时6-OHDA可能已漏入脑脊液,从而使下丘脑直接暴露于6-OHDA的毒性作用之下。