Shaikh M B, De Lanerolle N C, Siegel A
Departments of Neurosciences, New Jersey Medical School, Newark 07103, USA.
Brain Res. 1997 Aug 15;765(2):198-207. doi: 10.1016/s0006-8993(97)00433-2.
Recent studies have established that the expression of defensive rage behavior in the cat is mediated over a descending pathway from the medial hypothalamus to the dorsolateral quadrant of the midbrain periaqueductal gray matter (PAG). The present study was designed to determine the roles played by 5-HT1A and 5-HT2/1C receptors in this region of PAG in modulating defensive rage behavior elicited from the cat's medial hypothalamus. Monopolar stimulating electrodes were implanted into the medial hypothalamus from which defensive rage behavior could be elicited by electrical stimulation. During the course of the study, the 'hissing' component of the defensive rage response was used as a measure of defensive rage behavior. Cannula-electrodes were implanted into sites within the PAG from which defensive rage could also be elicited by electrical stimulation in order that 5-HT compounds could be microinjected into behaviorally identifiable regions of the PAG at a later time. Microinjections of the selective 5-HT1A agonist, (+)-8-hydroxy-dipropylaminotetralin hydrobromide (8-OHDPAT) (50 pmol, 2.0 and 3.0 nmol), into the PAG suppressed the hissing response in a dose-dependent manner. Administration of the selective 5-HT1A antagonist, 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl] ethyl]-N-2-pyridinyl-benzamide hydrochloride (p-MPPI) (1.5 and 3.0 nmol), blocked the suppressive effects of 8-OHDPAT upon hissing. In contrast, microinjections of the 5-HT2/1C receptor agonist (+)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride ((+)-DOI hydrochloride) (0.01, 1.0 and 1.5 nmol) facilitated the occurrence of hissing elicited from the medial hypothalamus in a dose-dependent manner. Immunohistochemical analysis revealed the presence of 5-HT axons and preterminals throughout the PAG, and in particular, in its dorsolateral aspect which receives major inputs from the medial hypothalamus in association with defensive rage behavior. The overall findings of the study provide evidence that activation of 5-HT1A and 5-HT2/1C receptors within the midbrain PAG differentially modulate the expression of defensive rage behavior elicited from the medial hypothalamus of the cat.
最近的研究表明，猫的防御性愤怒行为的表达是通过一条从中脑下丘脑到中脑导水管周围灰质（PAG）背外侧象限的下行通路介导的。本研究旨在确定PAG这一区域中的5-HT1A和5-HT2/1C受体在调节猫中脑下丘脑引发的防御性愤怒行为中所起的作用。将单极刺激电极植入中脑下丘脑，通过电刺激可引发防御性愤怒行为。在研究过程中，防御性愤怒反应的“嘶嘶声”成分被用作防御性愤怒行为的一种度量。将套管电极植入PAG内的部位，通过电刺激也可从该部位引发防御性愤怒，以便随后能够将5-羟色胺化合物微量注射到PAG中行为可识别的区域。向PAG微量注射选择性5-HT1A激动剂（+）-8-羟基-二丙基氨基四氢萘氢溴酸盐（8-OHDPAT）（50皮摩尔、2.0和3.0纳摩尔）以剂量依赖性方式抑制了嘶嘶声反应。给予选择性5-HT1A拮抗剂4-碘-N-[2-[4-（甲氧基苯基）-1-哌嗪基]乙基]-N-2-吡啶基-苯甲酰胺盐酸盐（p-MPPI）（1.5和3.0纳摩尔）可阻断8-OHDPAT对嘶嘶声的抑制作用。相反，向PAG微量注射5-HT2/1C受体激动剂（+）-1-（4-碘-2,5-二甲氧基苯基）-2-氨基丙烷盐酸盐（（+）-DOI盐酸盐）（0.01、1.0和1.5纳摩尔）以剂量依赖性方式促进了从中脑下丘脑引发的嘶嘶声的出现。免疫组织化学分析显示，5-羟色胺轴突和终末前纤维遍布整个PAG，特别是在其背外侧部分，该部分在防御性愤怒行为中接收来自中脑下丘脑的主要输入。该研究的总体结果提供了证据，即中脑PAG内5-HT1A和5-HT2/1C受体的激活对猫中脑下丘脑引发的防御性愤怒行为的表达具有不同的调节作用。
