Pratt Wayne E, Do Cardinal, Groome Alexandra M, Smith Alana J, Siegfried Allison C, Calafiore Camryn J
Department of Psychology, Wake Forest University, Winston-Salem, NC, United States.
Front Neurosci. 2025 Jul 14;19:1614819. doi: 10.3389/fnins.2025.1614819. eCollection 2025.
The nucleus accumbens is central for directing motivated behavior and is a key node in the neural circuitry that promotes eating in response to palatable diets. We examined the impact of intra-accumbens injections of a variety of homeostatic-related peptides (HRPs) on eating elicited by a sweetened fat diet, with or without co-administration of the prophagic mu-opioid agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO).
Rats received surgical placement of guide cannulas above the anterior medial nucleus accumbens. Non-restricted animals were then accustomed to 2-h daily access to a sweetened fat diet. Palatable eating was examined following intra-accumbens injections of one hypothalamic HRP, alone or with co-infusions of DAMGO.
Nucleus accumbens injections of neuropeptide Y (NPY) and Orexin-A significantly increased palatable eating. Cocaine- and amphetamine-related transcript (CART) reduced intake. When rats received co-stimulation of μ-opioid receptors, NPY and DAMGO had a synergistic effect on food intake, whereas Orexin-A initially disrupted eating on the palatable diet and had no additive effect with DAMGO by the end of the session. Neither agouti-related protein (AGRP), melanin concentrating hormone (MCH), alpha-melanocyte stimulating hormone (αMSH), nor the stress-related peptides corticotropin-releasing factor (CRF) or urocortin impacted intake, although MCH and CRF both affected eating in response to mu-opioid receptor stimulation dependent upon the dose.
These experiments offer insight into the regulation of hedonically motivated feeding by homeostatic- and stress-related inputs to the nucleus accumbens. This systematic examination suggests that the nucleus accumbens' role in promoting palatable eating is not independent of the homeostatic signals that reach it from the hypothalamus and other brain regions.
伏隔核对于引导动机性行为至关重要，并且是促进因美味食物而进食的神经回路中的关键节点。我们研究了向伏隔核内注射多种与内稳态相关的肽（HRP）对甜味高脂肪饮食引发的进食行为的影响，同时研究了是否联合给予促食欲的μ-阿片受体激动剂[D-丙氨酸2，N-甲基苯丙氨酸4，甘氨醇]-脑啡肽（DAMGO）。
大鼠接受手术，将引导套管置于伏隔核前内侧上方。然后让非限食动物每天有2小时的时间接触甜味高脂肪饮食。在向伏隔核内注射一种下丘脑HRP后，单独或联合注射DAMGO，检测美味食物的摄入量。
向伏隔核内注射神经肽Y（NPY）和食欲素A（Orexin-A）可显著增加美味食物的摄入量。可卡因和苯丙胺相关转录物（CART）减少了摄入量。当大鼠接受μ-阿片受体的联合刺激时，NPY和DAMGO对食物摄入量有协同作用，而食欲素A最初扰乱了美味食物的进食，到实验结束时与DAMGO没有相加作用。刺鼠相关蛋白（AGRP）、促黑素细胞激素（MCH）、α-黑素细胞刺激素（αMSH）以及与应激相关的肽促肾上腺皮质激素释放因子（CRF）或尿皮质素均未影响摄入量，尽管MCH和CRF在依赖剂量的情况下均会影响对μ-阿片受体刺激的进食反应。
这些实验为伏隔核通过内稳态和应激相关输入对享乐性动机性进食的调节提供了见解。这种系统性研究表明，伏隔核在促进美味食物进食方面的作用并非独立于从下丘脑和其他脑区传递至它的内稳态信号。
