Lu C L, Shaikh M B, Siegel A
Department of Neurosciences, New Jersey Medical School, Newark 07103.
Brain Res. 1992 May 22;581(1):123-32. doi: 10.1016/0006-8993(92)90351-9.
The present study tested the hypothesis that the pathway from the medial hypothalamus to the midbrain periaqueductal gray (PAG) subserving defensive rage behavior in the cat facilitates the occurrence of this response when elicited from the PAG by utilizing excitatory amino acids as a neurotransmitter or neuromodulator. Cannula electrodes were implanted into the PAG for the elicitation of defensive rage behavior as well as for microinjections of excitatory amino acid antagonists and N-methyl-D-aspartic acid (NMDA). Monopolar stimulating electrodes were also implanted into the medial hypothalamus from which this response could also be elicited and, when stimulated at subthreshold levels for elicitation of behavior, could also facilitate the occurrence of PAG elicited defensive rage. Initially, dual stimulation of the PAG and medial hypothalamus facilitated the occurrence of defensive rage elicited from the PAG. Then, the identical dual stimulation paradigm was repeated with the same current parameters following the infusion of various antagonists for different receptors into the PAG defensive rage sites. The results indicate that infusion of either kynurenic acid [(0.1-2.0 nmol), a non-selective excitatory amino acid receptor antagonist] or D-2-amino-7-phosphonoheptanoic acid (AP7) [(0.1-2.0 nmol), a specific NMDA receptor antagonist], produced a dose and time dependent blockade of the facilitatory effects of medial hypothalamic stimulation. In contrast, microinjections of relatively larger doses of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) [(4 nmol), a non-NMDA receptor (quisqualate and kainate) antagonist] or atropine [(4.4 nmol), a muscarinic receptor antagonist] had little effect upon medial hypothalamically elicited facilitation of the PAG response. In a second experiment, NMDA [0.1-1.0 nmol] was microinjected directly into PAG defensive rage sites in the absence of medial hypothalamic stimulation. In these animals, drug infusion mimicked the effects of dual stimulation by producing a dose and time dependent decrease in response latencies. A third experiment was designed to further test the hypothesis by neuroanatomical methods. Here, the retrograde label, Fluoro-Gold, was microinjected into defensive rage sites within the PAG and following a survival time of 5-6 days, the animals were sacrificed. The brains were then processed for immunocytochemical analysis of cells that immunoreact positively for aspartate and glutamate. The results indicated the presence of many retrogradely labelled and immunocytochemically positive cells within the rostro-caudal extent of the medial hypothalamus as well as others that were double labelled.(ABSTRACT TRUNCATED AT 400 WORDS)
猫体内从中脑内侧下丘脑到中脑导水管周围灰质（PAG）的、介导防御性愤怒行为的通路，在利用兴奋性氨基酸作为神经递质或神经调质从PAG引发该反应时，会促进这种反应的发生。将套管电极植入PAG，用于引发防御性愤怒行为以及微量注射兴奋性氨基酸拮抗剂和N-甲基-D-天冬氨酸（NMDA）。单极刺激电极也植入到内侧下丘脑，从中也可引发这种反应，并且当以低于引发行为的阈值水平进行刺激时，也能促进PAG引发的防御性愤怒的发生。最初，对PAG和内侧下丘脑进行双重刺激，促进了从PAG引发的防御性愤怒的发生。然后，在向PAG防御性愤怒位点注入针对不同受体的各种拮抗剂后，以相同的电流参数重复相同的双重刺激模式。结果表明，注入犬尿氨酸[（0.1 - 2.0纳摩尔），一种非选择性兴奋性氨基酸受体拮抗剂]或D-2-氨基-7-磷酸庚酸（AP7）[（0.1 - 2.0纳摩尔），一种特异性NMDA受体拮抗剂]，会产生剂量和时间依赖性的对内侧下丘脑刺激的促进作用的阻断。相比之下，微量注射相对大剂量的6-氰基-7-硝基喹喔啉-2,3-二酮（CNQX）[（4纳摩尔），一种非NMDA受体（quisqualate和海人藻酸）拮抗剂]或阿托品[（4.4纳摩尔），一种毒蕈碱受体拮抗剂]，对内侧下丘脑引发的PAG反应的促进作用影响很小。在第二个实验中，在没有内侧下丘脑刺激的情况下，将NMDA[0.1 - 1.0纳摩尔]直接微量注射到PAG防御性愤怒位点。在这些动物中，药物注入通过产生剂量和时间依赖性的反应潜伏期缩短，模拟了双重刺激的效果。第三个实验旨在通过神经解剖学方法进一步检验该假设。在此，将逆行标记物荧光金微量注射到PAG内的防御性愤怒位点，在存活5 - 6天后，处死动物。然后对大脑进行处理，用于对天冬氨酸和谷氨酸免疫反应呈阳性的细胞进行免疫细胞化学分析。结果表明，在内侧下丘脑的头 - 尾范围内存在许多逆行标记且免疫细胞化学呈阳性的细胞，以及其他双重标记的细胞。（摘要截取自400字）
