Department of Physiology/Endocrinology, The Sahlgrenska Academy at the University of Gothenburg, SE-405 30 Gothenburg, Sweden.
Addict Biol. 2010 Jul;15(3):304-11. doi: 10.1111/j.1369-1600.2010.00216.x. Epub 2010 May 6.
We investigated whether ghrelin action at the level of the ventral tegmental area (VTA), a key node in the mesolimbic reward system, is important for the rewarding and motivational aspects of the consumption of rewarding/palatable food. Mice with a disrupted gene encoding the ghrelin receptor (GHS-R1A) and rats treated peripherally with a GHS-R1A antagonist both show suppressed intake of rewarding food in a free choice (chow/rewarding food) paradigm. Moreover, accumbal dopamine release induced by rewarding food was absent in GHS-R1A knockout mice. Acute bilateral intra-VTA administration of ghrelin increased 1-hour consumption of rewarding food but not standard chow. In comparison with sham rats, VTA-lesioned rats had normal intracerebroventricular ghrelin-induced chow intake, although both intake of and time spent exploring rewarding food was decreased. Finally, the ability of rewarding food to condition a place preference was suppressed by the GHS-R1A antagonist in rats. Our data support the hypothesis that central ghrelin signaling at the level of the VTA is important for the incentive value of rewarding food.
我们研究了生长激素释放肽（ghrelin）在腹侧被盖区（VTA）水平的作用，VTA 是中边缘奖励系统的关键节点，对于奖励性/美味食物消费的奖励和动机方面是否重要。缺乏编码生长激素释放肽受体（GHS-R1A）的基因的小鼠和外周给予 GHS-R1A 拮抗剂的大鼠在自由选择（chow/奖励性食物）范式中都表现出奖励性食物摄入减少。此外，GHS-R1A 基因敲除小鼠的伏隔核多巴胺释放被抑制。急性双侧 VTA 内给予生长激素会增加 1 小时内奖励性食物的摄入量，但不会增加标准食物的摄入量。与假手术大鼠相比，VTA 损伤大鼠的脑室注射生长激素引起的标准食物摄入量正常，尽管奖励性食物的摄入量和探索时间减少。最后，GHS-R1A 拮抗剂抑制了奖励性食物形成位置偏好的能力。我们的数据支持这样的假设，即 VTA 水平的中枢生长激素释放肽信号对于奖励性食物的激励价值很重要。
