Geuzaine Annabelle, Tyhon Amélie, Grisar Thierry, Brabant Christian, Lakaye Bernard, Tirelli Ezio
Département de Psychologie, Cognition et Comportement, University of Liège, B-4000 Liège, Belgium.
GIGA-Neurosciences, University of Liège, B-4000 Liège, Belgium.
Behav Brain Res. 2014 Apr 1;262:14-20. doi: 10.1016/j.bbr.2013.12.052. Epub 2014 Jan 8.
Chronic food restriction (FR) and maintenance of low body weight have long been known to increase the rewarding and motor-activating effects of addictive drugs. However, the neurobiological mechanisms through which FR potentiates drug reward remain largely unknown. Melanin-concentrating hormone (MCH) signaling could be one of these mechanisms since this peptide is involved in energy homeostasis and modulates mesolimbic dopaminergic transmission. The purpose of the present study was to test this hypothesis by investigating the impact of FR on amphetamine reward in wild-type (WT) and knockout mice lacking the melanin-concentrating hormone receptor-1 (MCHR1-KO). The rewarding effects of amphetamine (0.75-2.25 mg/kg, i.p.) were measured with the conditioned place preference (CPP) technique. The food of the mice was restricted to maintain their body weight at 80-85% of their free-feeding (FF) weight throughout the entire CPP experiment. Locomotor activity of the animals was recorded during the conditioning sessions. Our results show that locomotion of all the food-restricted mice treated with saline or amphetamine increased over the sessions whatever the genotype. On the place preference test, the amplitude of CPP induced by 0.75 mg/kg amphetamine was higher in food restricted WT mice than in free-fed WT mice and food restricted MCHR1-KO mice. However, FR did not affect amphetamine reward in MCHR1-KO mice. The present results indicate that MCH signaling could be involved in the ability of FR to increase amphetamine-induced CPP.
长期以来，人们一直知道慢性食物限制（FR）和维持低体重会增强成瘾药物的奖赏和运动激活作用。然而，FR增强药物奖赏的神经生物学机制在很大程度上仍不清楚。黑色素浓缩激素（MCH）信号传导可能是其中一种机制，因为这种肽参与能量稳态并调节中脑边缘多巴胺能传递。本研究的目的是通过研究FR对野生型（WT）和缺乏黑色素浓缩激素受体-1（MCHR1-KO）的基因敲除小鼠中苯丙胺奖赏的影响来验证这一假设。用条件性位置偏爱（CPP）技术测量苯丙胺（0.75-2.25mg/kg，腹腔注射）的奖赏作用。在整个CPP实验过程中，限制小鼠的食物摄入，使其体重维持在自由进食（FF）体重的80-85%。在条件训练期间记录动物的运动活动。我们的结果表明，无论基因型如何，在训练过程中，所有接受盐水或苯丙胺治疗的食物限制小鼠的运动都增加了。在位置偏爱测试中，0.75mg/kg苯丙胺诱导的CPP幅度在食物限制的WT小鼠中高于自由进食的WT小鼠和食物限制的MCHR1-KO小鼠。然而，FR对MCHR1-KO小鼠的苯丙胺奖赏没有影响。目前的结果表明，MCH信号传导可能参与了FR增加苯丙胺诱导的CPP的能力。
