Wilson John D, Nicklous Danielle M, Aloyo Vincent J, Simansky Kenny J
Dept. of Pharmacology and Physiology, Drexel Univ. College of Medicine, Mailstop 488, 245 N. 15th St., Philadelphia, PA 19102-1192, USA.
Am J Physiol Regul Integr Comp Physiol. 2003 Nov;285(5):R1055-65. doi: 10.1152/ajpregu.00108.2003.
The pontine parabrachial nucleus (PBN) has been implicated in regulating ingestion and contains opioids that promote feeding elsewhere in the brain. We tested the actions of the selective mu-opioid receptor (mu-OR) agonist [d-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO) in the PBN on feeding in male rats with free access to food. Infusing DAMGO (0.5-4.0 nmol/0.5 microl) into the lateral parabrachial region (LPBN) increased food intake. The hyperphagic effect was anatomically specific to infusions within the LPBN, dose and time related, and selective for ingestion of chow compared with (nonnutritive) kaolin. The nonselective opioid antagonist naloxone (0.1-10.0 nmol intra-PBN) antagonized DAMGO-induced feeding, with complete blockade by 1.0 nmol and no effect on baseline. The highly selective mu-opioid antagonist d-Phe-Cys-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP; 1.0 nmol) also prevented this action of DAMGO, but the kappa-antagonist nor-binaltorphimine did not. Naloxone and CTAP (10.0 nmol) decreased intake during scheduled feeding. Thus stimulating mu-ORs in the LPBN increases feeding, whereas antagonizing these sites inhibits feeding. Together, our results implicate mu-ORs in the LPBN in the normal regulation of food intake.
脑桥臂旁核(PBN)与调节摄食有关,并且含有能促进大脑其他部位进食的阿片类物质。我们测试了选择性μ-阿片受体(μ-OR)激动剂[D-丙氨酸2,N-甲基苯丙氨酸4,甘氨酸5-醇]脑啡肽(DAMGO)在PBN中对自由获取食物的雄性大鼠进食行为的影响。向外侧臂旁区域(LPBN)注入DAMGO(0.5 - 4.0 nmol/0.5微升)会增加食物摄入量。这种贪食效应在解剖学上特定于LPBN内的注射,与剂量和时间相关,并且与(无营养的)高岭土相比,对食物摄取具有选择性。非选择性阿片拮抗剂纳洛酮(0.1 - 10.0 nmol,脑桥臂旁核内注射)可拮抗DAMGO诱导的进食,1.0 nmol时完全阻断,对基线无影响。高选择性μ-阿片拮抗剂D-苯丙氨酸-半胱氨酸-色氨酸-精氨酸-苏氨酸-青霉胺-苏氨酸-氨基(CTAP;1.0 nmol)也可阻止DAMGO的这种作用,但κ-拮抗剂去甲二氢吗啡酮则无此作用。纳洛酮和CTAP(10.0 nmol)在定时喂食期间会减少摄入量。因此,刺激LPBN中的μ-OR会增加进食,而拮抗这些部位则会抑制进食。总之,我们的结果表明LPBN中的μ-OR参与食物摄入的正常调节。