Heinrichs S C, Menzaghi F, Pich E M, Hauger R L, Koob G F
Scripps Research Institute, Department of Neuropharmacology, La Jolla, CA 92037.
Brain Res. 1993 May 14;611(1):18-24. doi: 10.1016/0006-8993(93)91771-j.
Central administration of neuropeptide Y (NPY) exerts a potent orexigenic effect in rats, whereas injection of corticotropin-releasing factor (CRF) suppresses food intake. Anatomical evidence of NPY-containing terminals located in close proximity to CRF-containing neurons and terminals of the hypothalamus and amygdala suggests possible interactions of these neuropeptide systems in food-intake regulation. The present study examined the effect of local administration of the CRF antagonist, alpha-helical CRF9-41, or peripheral treatment with dexamethasone on NPY-induced hyperphagia. Injection of a 250-ng dose of alpha-hel CRF within the paraventricular nucleus (PVN) of the hypothalamus significantly potentiated the feeding induced by a 500-ng dose of NPY injected into the same locus. In contrast, feeding induced by administration of the 500-ng dose of NPY into the ventromedial hypothalamus (VMH) was not modified by intra-VMH pre-treatment with a 250-ng dose of CRF antagonist. No effects of NPY or alpha-hel CRF on feeding were observed after administration into the central nucleus of the amygdala. Systemic pre-treatment with the synthetic glucocorticoid dexamethasone at a dose known to downregulate the function of CRF neurons in the PVN (100 micrograms/kg) enhanced feeding induced by intra-PVN administration of a 500-ng dose of NPY. These results suggest that hypothalamic CRF systems in the PVN exert inhibitory control over NPY-induced food intake.
中枢给予神经肽Y（NPY）可在大鼠中发挥强大的促食欲作用，而注射促肾上腺皮质激素释放因子（CRF）则会抑制食物摄入。下丘脑和杏仁核中含NPY的终末与含CRF的神经元和终末位置紧邻的解剖学证据表明，这些神经肽系统在食物摄入调节中可能存在相互作用。本研究检测了局部给予CRF拮抗剂α-螺旋CRF9-41或地塞米松外周治疗对NPY诱导的摄食过多的影响。在下丘脑室旁核（PVN）内注射250 ng剂量的α-螺旋CRF，可显著增强向同一部位注射500 ng剂量NPY所诱导的进食。相反，向腹内侧下丘脑（VMH）注射500 ng剂量NPY所诱导的进食，并未因预先在VMH内注射250 ng剂量的CRF拮抗剂而改变。向杏仁核中央核注射后，未观察到NPY或α-螺旋CRF对进食有影响。以已知可下调PVN中CRF神经元功能的剂量（100 μg/kg）对合成糖皮质激素地塞米松进行全身预处理，可增强向PVN内注射500 ng剂量NPY所诱导的进食。这些结果表明，PVN中的下丘脑CRF系统对NPY诱导的食物摄入发挥抑制性控制作用。
