Department of Psychology, Center for Studies in Behavioral Neurobiology, Group de Recherche en neurobiologie comportementale, Concordia University, Montreal, QC, Canada.
Addict Biol. 2012 May;17(3):613-22. doi: 10.1111/j.1369-1600.2011.00396.x. Epub 2011 Oct 13.
Food deprivation (FD) or restriction augments the locomotor activating and reinforcing effects of drugs of abuse. It has been proposed that these effects might be mediated by FD-induced increase in plasma levels of ghrelin, a 28-amino acid orexigenic peptide demonstrated to functionally interact with the mesolimbic dopaminergic system. However, a role for ghrelin has been demonstrated only with psychostimulant drugs and alcohol associated behaviors. We therefore examined the role of ghrelin in ongoing heroin self-administration and FD-induced reinstatement of extinguished heroin seeking. As expected, infusions of ghrelin [0.0, 1.5 and 3.0 µg/rat, intracerebroventricular (i.c.v.)] produced increases in breakpoints on a progressive ratio schedule of heroin reinforcement. In contrast, central administration of a ghrelin receptor antagonist, [D-Lys-3]-GHRP-6 (0.0, or 20.0 µg/rat, i.c.v.) had no effect on ongoing heroin self-administration under a fixed-ratio 1 schedule, or on FD-induced reinstatement of heroin seeking. These results suggest that signals mediated through ghrelin receptors play a limited role in FD-induced augmentation of heroin reinforcement and reinstatement of extinguished heroin seeking.
禁食（FD）或限制会增强滥用药物的运动激活和强化作用。有人提出，这些作用可能是由 FD 引起的血浆胃饥饿素水平升高介导的，胃饥饿素是一种 28 个氨基酸的食欲肽，已被证明与中脑边缘多巴胺能系统有功能相互作用。然而，胃饥饿素的作用仅在精神兴奋剂药物和与酒精相关的行为中得到了证明。因此，我们研究了胃饥饿素在持续海洛因自我给药和 FD 诱导的已熄灭海洛因寻求复燃中的作用。正如预期的那样，胃饥饿素[0.0、1.5 和 3.0 µg/大鼠，侧脑室（i.c.v.）]输注会增加海洛因强化的递增比率方案中的断点。相比之下，中央给予胃饥饿素受体拮抗剂[D-Lys-3]-GHRP-6[0.0 或 20.0 µg/大鼠，i.c.v.]对固定比率 1 方案下的持续海洛因自我给药或 FD 诱导的已熄灭海洛因寻求复燃没有影响。这些结果表明，通过胃饥饿素受体介导的信号在 FD 诱导的海洛因强化增强和已熄灭的海洛因寻求复燃中发挥有限的作用。
