Coscina D V, Feifel D, Nobrega J N, Currie P J
Section of Biopsychology, Clarke Institute of Psychiatry, University of Toronto, Ontario, Canada.
Am J Physiol. 1994 May;266(5 Pt 2):R1562-7. doi: 10.1152/ajpregu.1994.266.5.R1562.
Previous research has shown that systemic injections of the nonselective serotonin (5-HT) antagonist metergoline (MET) can stimulate feeding in both rats and humans. Five experiments were conducted to determine if this drug would elicit feeding in otherwise satiated rats after direct injections into the brain. In experiment 1, intraventricular infusions of 100 nmol MET produced reliable enhancements of feeding for 1 h compared with control infusions of a 5% tartaric acid (vehicle) solution. In experiment 2, a dose-response study of 0, 50, 100, and 150 nmol MET intraventricularly revealed that both 100 and 150 nmol doses reliably enhanced 1-h feeding, whereas 50 nmol did not. In experiment 3, tests of 90-min locomotor activity and water intake in the absence of food revealed that 100 nmol MET intraventricularly did not modify either behavior compared with vehicle infusions, suggesting a degree of feeding specificity to this effect. In an attempt to determine the site of intraventricular MET effects on feeding, experiment 4 tested 1-h feeding responses after 0, 5, 10, 20, 40, or 60 nmol MET were infused unilaterally into the paraventricular nucleus (PVN) of the hypothalamus. No reliable feeding was induced at any of these drug doses, although injections of 30 nmol norepinephrine (NE) were effective in doubling food intake. Experiment 5 further showed that bilateral infusions of 50 nmol MET in each PVN (total dose, 100 nmol) were ineffective in altering 1-h feeding. This contrasted markedly to the high potency of 15 nmol NE per site (total dose, 30 nmol), which elicited fivefold greater feeding than control infusions.(ABSTRACT TRUNCATED AT 250 WORDS)
先前的研究表明,全身性注射非选择性血清素(5-羟色胺,5-HT)拮抗剂美替拉酮(MET)可刺激大鼠和人类进食。进行了五项实验,以确定该药物直接注射到大脑后,是否会促使原本已饱足的大鼠进食。在实验1中,与注射5%酒石酸(赋形剂)溶液的对照输注相比,脑室内注入100纳摩尔MET可使进食量在1小时内得到可靠增加。在实验2中,对脑室内注射0、50、100和150纳摩尔MET进行剂量反应研究,结果显示100和150纳摩尔剂量均能可靠地增加1小时的进食量,而50纳摩尔剂量则无此效果。在实验3中,对无食物情况下90分钟的运动活动和饮水量进行测试,结果显示与注射赋形剂相比,脑室内注射100纳摩尔MET对这两种行为均无影响,表明这种效应具有一定程度的进食特异性。为了确定脑室内MET对进食产生影响的部位,实验4测试了向下丘脑室旁核(PVN)单侧注入0、5、10、20、40或60纳摩尔MET后的1小时进食反应。尽管注射30纳摩尔去甲肾上腺素(NE)能使食物摄入量翻倍,但这些药物剂量均未可靠地诱导进食。实验5进一步表明,在每个PVN双侧注入50纳摩尔MET(总剂量为100纳摩尔)对改变1小时的进食量无效。这与每侧15纳摩尔NE的高效力形成鲜明对比(总剂量为30纳摩尔),后者引起的进食量比对照输注大五倍。(摘要截选至250字)