Contribution of caudal brainstem to d-fenfluramine anorexia
Contribution of caudal brainstem to d-fenfluramine anorexia
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DOI：
10.1007/s002130050253
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发表时间：
1997-04-01
影响因子：
3.4
通讯作者：
Kaplan, JM
中科院分区：
文献类型：
--
作者：
Grill, HJ;Donahey, JCK;Kaplan, JM
中枢5-HT底物可能介导的d-fenfluramine（d-FEN）的全身给药的兴奋作用，前脑中的那些受到了最多的关注。作为一个对立面，这个前脑的重点，我们评估了尾脑干基板的d-FEN的神经传导作用的贡献。采用了两种实验方案。在一项研究中，我们比较了完整和慢性上丘去脑（CD）大鼠对全身给予d-FEN的摄食反应（口服12.5%葡萄糖）。在另一个实验中，通过第四次侧脑室（ICV）注射给予d-FEN，以确定是否可以获得剂量相关的口内摄入抑制。在用d-FEN（0-8 mg/kg，在测试前20分钟IP递送）处理的CD大鼠中获得了口内摄入的剂量依赖性抑制。CD大鼠的阈值剂量是其完整对照组的2 - 3倍，但两组剂量-反应曲线的动态范围重叠，下降斜率相似，最大摄入抑制相当。第四ICV管理d-FEN在完整的大鼠产生了剂量相关的抑制口内摄入。当大鼠从喷口饮用12.5%葡萄糖溶液时，第四次ICV d-FEN（30 mg）也抑制了摄入。通过全身给予5-羟色胺拮抗剂甲麦角林（0.4 mg/kg; IP），第四次ICV d-FEN治疗后口内摄入量减少部分减弱。CD结果表明尾脑干受体在介导对系统性d-FEN的摄取抑制反应中的充分性。第四ICV的结果进一步表明，5-HT受体在尾脑干发挥了重要作用，在正常的饮食量控制在神经系统完整的大鼠。
Of the central 5-HT substrates that may mediate the anorexic actions of systemically administered d-fenfluramine (d-FEN), those in the forebrain have received the most attention. As a counterpoint to this forebrain focus, we evaluated the contribution of caudal brainstem substrates to the anorexic action of d-FEN. Two experimental protocols were employed. In one we compared the feeding response (intra-oral intake of 12.5% glucose) of intact and chronic supracollicular decerebrate (CD) rats to systemic administration of d-FEN. In the other, d-FEN was administered via fourth intracerebroventricular (ICV) injection to determine whether a dose-related suppression of intra-oral intake could be obtained. A dose-dependent suppression of intra-oral intake was obtained in the CD rat treated with d-FEN (0-8 mg/kg, delivered IP 20 min before testing). The threshold dose was two to three times higher in CD rats than in their intact controls, but the dynamic range of the dose-response curves of the two groups were overlapping with similar slopes of decline and with comparable maximal intake suppression. Fourth ICV administration of d-FEN in the intact rat yielded a dose-related suppression of intra-oral intake. Intake was also suppressed by fourth ICV d-FEN (30 mg) when rats drank 12.5% glucose solution from a spout. The reduced intra-oral intake following fourth ICV d-FEN treatment was partially attenuated by the systemic administration of the serotonin antagonist metergoline (0.4 mg/kg; IP). The CD results demonstrate the sufficiency of caudal brainstem receptors in mediating intake suppressive responses to systemic d-FEN. The fourth ICV results suggest further that 5-HT receptors in the caudal brainstem play a significant role in normal meal size control in the neurologically intact rat.