Department of Psychology, Wake Forest University, Winston-Salem, NC 27109, United States.
Behav Brain Res. 2011 Jun 1;219(2):265-72. doi: 10.1016/j.bbr.2011.01.024. Epub 2011 Jan 22.
The high attrition rates for dietary interventions aimed at promoting a healthier body mass may be caused, at least in part, by constant exposure to environmental stimuli that are associated with palatable foods. In both humans and animals, conditioned stimuli (CSs) that signal reward availability reliably reinstate food- and drug-seeking behaviors. The nucleus accumbens (NAcc) is critically involved in the cue-evoked reinstatement of food-seeking, but the role of individual neurotransmitter systems within the NAcc remains to be determined. These experiments tested the effects of intra-accumbal pharmacological manipulations of dopamine (DA) D(1) and D(2) receptors, mu-opioid receptors, or serotonin (5-HT) receptors on cue-evoked relapse to food-seeking. Rats were trained to lever press for sucrose pellets and the concurrent presentation of a light-tone CS. Once training was complete, lever-pressing was extinguished in the absence of either sucrose or CS presentation. Once each rat had reached extinction criterion, they received two reinstatement sessions in which lever pressing was renewed by response-contingent presentation of the CS. Prior to each reinstatement test, rats received NAcc microinfusions of saline or the selective D(1) receptor antagonist SCH 23390, the D(2) receptor antagonist raclopride, the mu-opioid receptor agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO), or 5-HT hydrogen maleate. Compared to saline test days, intra-accumbens infusions of SCH 23390 (1 μg/0.5 μL), raclopride (1 μg/0.5 μL), or DAMGO (0.25 μg/0.5 μL) effectively blocked the cue-evoked reinstatement of food-seeking. In contrast, stimulation of serotonin (5-HT) receptors by 5-HT hydrogen maleate (5 μg/0.5 μL) had no effect on cue-induced reinstatement. These novel data support roles for NAcc DA D(1), D(2), and mu-opioid receptors in the cue-evoked reinstatement of food seeking.
旨在促进更健康体重的饮食干预措施的高淘汰率可能至少部分是由于持续暴露于与美味食物相关的环境刺激。在人类和动物中，信号奖励可用性的条件刺激 (CS) 可靠地重新恢复食物和药物寻求行为。伏隔核 (NAcc) 在内源性线索诱发的食物寻求中起着至关重要的作用，但 NAcc 内个体神经递质系统的作用仍有待确定。这些实验测试了 NAcc 内多巴胺 (DA) D(1) 和 D(2) 受体、μ-阿片受体或 5-羟色胺 (5-HT) 受体的药理学操纵对线索诱发的食物寻求复吸的影响。大鼠接受训练以按压杠杆获取蔗糖丸，并同时呈现灯光 CS。一旦训练完成，在没有蔗糖或 CS 呈现的情况下，按压杠杆会被熄灭。一旦每只老鼠达到熄灭标准，它们就会进行两次复吸测试，其中通过对 CS 的反应依存呈现来恢复按压杠杆。在每次复吸测试之前，大鼠接受 NAcc 内微量注射盐水或选择性 D(1) 受体拮抗剂 SCH 23390、D(2) 受体拮抗剂 raclopride、μ-阿片受体激动剂 [D-Ala2，N-MePhe4，Gly-ol]-enkephalin (DAMGO) 或 5-HT 顺丁烯二酸。与盐水测试日相比，NAcc 内注射 SCH 23390（1μg/0.5μL）、raclopride（1μg/0.5μL）或 DAMGO（0.25μg/0.5μL）可有效阻断线索诱发的食物寻求复吸。相比之下，5-HT 顺丁烯二酸（5μg/0.5μL）刺激 5-HT 受体对线索诱导的复吸没有影响。这些新数据支持 NAcc DA D(1)、D(2) 和 μ-阿片受体在线索诱发的食物寻求复吸中的作用。
