Wellman P J, Davies B T
Department of Psychology, Texas A&M University, College Station 77843.
Appetite. 1991 Oct;17(2):121-8. doi: 10.1016/0195-6663(91)90067-3.
Rats were treated with the alpha-2 agonist clonidine (4, 20 and 50 nMol) and with the alpha-1 agonist 1-phenylephrine (50, 100, 200 and 400 nMol). Phenylpropanolamine (PPA) is a phenythylamine anorectic drug that exerts direct agonist effects predominantly on alpha-1 adrenergic receptors, with some alpha-2 adrenergic activity. We recently reported that injection of PPA significantly suppressed feeding in rats. Prior studies have noted that into the paraventricular hypothalamus (PVN) microinjections of the alpha-2 adrenergic receptor agonist clonidine into the PVN induced feeding behavior in satiated rats. However, the effect on feeding of administration of alpha-1 adrenergic agonists within the PVN remains unknown. In the present study, unilateral guide cannulae aimed at the PVN were surgically implanted in adult male rats. In an initial 60 min feeding test conducted under free-feeding ("non-deprived") conditions, each rat was found to eat significantly more food after injection of 25 nMol norepinephrine (NE) into the PVN. In subsequent tests, the feeding increased significantly to 4 nMol clonidine; however, feeding was suppressed by 50 nMol clonidine. Food intake after 20 nMol clonidine was not significantly different from that recorded after vehicle. In contrast, phenylephrine (100-400 nMol) reliably suppressed feeding behavior. In the final phase of the study, the rats ate significantly less food after injection of 160 nMol PPA into the PVN but consumed significantly more food after a final injection of 25 nMol NE into the PVN. These results suggest that the anorexic action of PPA may be linked to activation of alpha-1 adrenergic receptors within the PVN.
用α-2激动剂可乐定（4、20和50纳摩尔）以及α-1激动剂去氧肾上腺素（50、100、200和400纳摩尔）对大鼠进行处理。苯丙醇胺（PPA）是一种苯乙胺类食欲抑制剂药物，主要对α-1肾上腺素能受体发挥直接激动剂作用，同时具有一些α-2肾上腺素能活性。我们最近报道，注射PPA可显著抑制大鼠进食。先前的研究指出，向饱足大鼠的室旁下丘脑（PVN）微量注射α-2肾上腺素能受体激动剂可乐定可诱导进食行为。然而，PVN内注射α-1肾上腺素能激动剂对进食的影响仍不清楚。在本研究中，将针对PVN的单侧引导套管手术植入成年雄性大鼠体内。在自由进食（“非剥夺”）条件下进行的初始60分钟进食试验中，发现每只大鼠在向PVN注射25纳摩尔去甲肾上腺素（NE）后进食量显著增加。在随后的试验中，进食量在注射4纳摩尔可乐定时显著增加；然而，50纳摩尔可乐定则抑制进食。20纳摩尔可乐定后的食物摄入量与注射赋形剂后的记录无显著差异。相比之下，去氧肾上腺素（100 - 400纳摩尔）可靠地抑制进食行为。在研究的最后阶段，大鼠在向PVN注射160纳摩尔PPA后进食量显著减少，但在最后一次向PVN注射25纳摩尔NE后进食量显著增加。这些结果表明，PPA的厌食作用可能与PVN内α-1肾上腺素能受体的激活有关。
