Center for Neuropharmacology and Neuroscience MC-136, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USA.
Psychopharmacology (Berl). 2011 May;215(2):247-56. doi: 10.1007/s00213-010-2132-0. Epub 2011 Jan 6.
18-methoxycoronaridine (18-MC), a selective antagonist of α3β4 nicotinic receptors, has been previously shown, in rats, to reduce the self-administration of several drugs of abuse, reduce operant responding for sucrose, and prevent the development of sucrose-induced obesity. It has become increasingly apparent that there is a significant overlap between the systems regulating drug reward and food intake, therefore, we investigated whether 18-MC might modulate the effects of ghrelin, one of several orexigenic peptides recently implicated in both feeding and drug reward.
In female Sprague-Dawley rats, we determined whether acute 18-MC treatment would reduce both ghrelin-induced increases in sucrose intake and ghrelin-elicited increases in accumbal dopamine levels.
Pretreatment with 18-MC (20 mg/kg, i.p.), given prior to the administration of ghrelin (1 μg, lateral ventricle), blocked ghrelin-induced increases in sucrose (5%) intake in a two-bottle open access paradigm. Using in vivo microdialysis, 18-MC (both 20 and 40 mg/kg) prevented ghrelin (2 μg, intraventral tegmental area)-induced increases in extracellular dopamine in the nucleus accumbens. 18-MC had no effect on deposition of fat or on serum levels of glucose, triglycerides, and cholesterol in ghrelin-treated rats.
The present results suggest that one potential mechanism by which 18-MC exerts its effects on palatable food consumption is via modulation of ghrelin's effects.
18-甲氧基考尼丁（18-MC）是一种选择性α3β4 烟碱型乙酰胆碱受体拮抗剂，先前已在大鼠中显示，它可以减少几种滥用药物的自我给药，减少蔗糖的操作性反应，并预防蔗糖诱导的肥胖。越来越明显的是，调节药物奖赏和食物摄入的系统之间存在显著重叠，因此，我们研究了 18-MC 是否可能调节 ghrelin 的作用，ghrelin 是最近在进食和药物奖赏中都涉及的几种食欲肽之一。
在雌性 Sprague-Dawley 大鼠中，我们确定急性 18-MC 处理是否会降低 ghrelin 诱导的蔗糖摄入增加和伏隔核多巴胺水平增加。
在给予 ghrelin（1 μg，侧脑室）之前，预先给予 18-MC（20 mg/kg，ip），可阻断 ghrelin 诱导的蔗糖（5%）摄入增加。使用体内微透析，18-MC（20 和 40 mg/kg 两种剂量）可预防 ghrelin（2 μg，腹侧被盖区）诱导的伏隔核细胞外多巴胺增加。18-MC 对 ghrelin 处理大鼠的脂肪沉积或血清葡萄糖、甘油三酯和胆固醇水平没有影响。
本研究结果表明，18-MC 对美味食物消费的影响的一种潜在机制是通过调节 ghrelin 的作用。
