Viggiano An, Monda M, Viggiano Al, Fuccio F, De Luca B
Section of Human Physiology, Department of Experimental Medicine, Second University of Naples, Naples, Italy.
Acta Physiol Scand. 2004 Sep;182(1):89-94. doi: 10.1111/j.1365-201X.2004.01298.x.
Hypocretin 1 is an hypothalamic neuropeptide that induces an increase in food intake when administered into the cerebral lateral ventricle. As it is well known that the medial hypothalamus (MH) is involved in the feeding behaviour also through GABAergic circuits, the aim of this experiment was to investigate the effect of an hypocretin 1 intracerebroventricular (icv) injection on the extracellular levels of GABA in the MH.
GABA levels in the MH were evaluated in six rats by microdialysis and high performance liquid chromatography-electrochemical detection 30 min before and every 30 min for an over all period of 6 h after an icv injection of hypocretin 1. The same procedure was used in another group of six rats but saline was injected into the lateral ventricle as control.
The results show that extracellular GABA increases in the MH after the injection of hypocretin 1 at 60 min and at 3 h after the injection.
This finding suggests a possible mechanism by which hypocretin 1 should induce hyperphagia in the first hour after injection. As it is already known that the inhibition of the MH by injection of GABA causes an increase of food intake, it is possible that hypocretin 1 causes an increase in food intake by increasing the GABA release in the MH. The lack of an increase in the GABA level after the fourth hour is consistent with the lack of an increase in food intake at this time, as we observed in previous experiments. The finding of a biphasic increase in the GABA level, at 60 min and at 3 h, was unexpected and should be further investigated.
食欲素1是一种下丘脑神经肽，当注入大脑侧脑室时会导致食物摄入量增加。众所周知，内侧下丘脑（MH）也通过γ-氨基丁酸（GABA）能回路参与进食行为，本实验的目的是研究脑室内注射食欲素1对内侧下丘脑GABA细胞外水平的影响。
通过微透析和高效液相色谱-电化学检测法，在6只大鼠脑室内注射食欲素1前30分钟以及注射后6小时内每隔30分钟评估内侧下丘脑的GABA水平。另一组6只大鼠采用相同程序，但向侧脑室内注射生理盐水作为对照。
结果显示，注射食欲素1后60分钟和3小时，内侧下丘脑的细胞外GABA增加。
这一发现提示了一种可能的机制，即食欲素1在注射后第一小时内应诱导食欲亢进。由于已知注射GABA抑制内侧下丘脑会导致食物摄入量增加，因此食欲素1可能通过增加内侧下丘脑的GABA释放来导致食物摄入量增加。第四小时后GABA水平未升高与此时食物摄入量未增加一致，正如我们在先前实验中观察到的那样。在60分钟和3小时时GABA水平出现双相增加这一发现出乎意料，应进一步研究。
