Urbanavicius Jessika, Lagos Patricia, Torterolo Pablo, Scorza Cecilia
aLaboratory of Cell Biology bDepartment of Experimental Neuropharmacology, Instituto de Investigaciones Biológicas Clemente Estable cDepartment of Physiology, Facultad de Medicina, Montevideo, Uruguay.
Behav Pharmacol. 2014 Aug;25(4):316-24. doi: 10.1097/FBP.0000000000000056.
Melanin-concentrating hormone (MCH) administered within the rat dorsal raphe nucleus (DRN) has been shown to elicit prodepressive behaviors in the forced-swim test. The present study was designed to evaluate the time course (30 and 60 min) and dose dependence (25-100 ng) of this effect, and whether it would be antagonized by an intra-DRN microinjection of the MCH-1 receptor antagonist ATC0175 (ATC, 1 mmol/l) or intraperitoneal pretreatment with the noradrenergic antidepressant nortriptyline (20 mg/kg). The results showed that the behavioral effect of MCH was time and dose dependent as immobility was increased, and climbing decreased, only by the 50 ng MCH dose at T30. The effect was mediated by MCH-1 receptors as a significant blockade of this behavioral response was observed in ATC-pretreated animals. ATC did not by itself modify animal behavior. Nortriptyline also prevented the prodepressive-like effect of MCH. Concomitantly, the effect of MCH (50 ng) at T30 on anxiety-related behaviors was assessed using the elevated plus-maze. Interestingly, these behaviors were unchanged. In conclusion, MCH administration within the DRN elicits, through the MCH-1 receptor, a depression-related behavior that is not accompanied by changes in anxiety and that is prevented by a noradrenergic antidepressant.
已证明在大鼠中缝背核（DRN）内注射黑色素浓缩激素（MCH）会在强迫游泳试验中引发促抑郁行为。本研究旨在评估这种效应的时间进程（30分钟和60分钟）和剂量依赖性（25 - 100纳克），以及DRN内微量注射MCH - 1受体拮抗剂ATC0175（ATC，1毫摩尔/升）或用去甲肾上腺素能抗抑郁药去甲替林（20毫克/千克）进行腹腔预处理是否会拮抗这种效应。结果表明，MCH的行为效应具有时间和剂量依赖性，因为仅在T30时50纳克MCH剂量会增加不动时间并减少攀爬时间。这种效应是由MCH - 1受体介导的，因为在ATC预处理的动物中观察到这种行为反应被显著阻断。ATC本身不会改变动物行为。去甲替林也能预防MCH的促抑郁样效应。同时，使用高架十字迷宫评估了T30时MCH（50纳克）对焦虑相关行为的影响。有趣的是，这些行为没有变化。总之，在DRN内注射MCH会通过MCH - 1受体引发一种与抑郁相关的行为，这种行为不伴有焦虑变化，并且会被去甲肾上腺素能抗抑郁药预防。
