Cousens Graham A, Beckley Jacob T
Department of Psychology and Program in Cognitive and Neuroscience Studies, Macalester College, 1600 Grand Avenue, Saint Paul, Minnesota 55105, United States.
Behav Brain Res. 2007 Jul 19;181(1):127-35. doi: 10.1016/j.bbr.2007.03.036. Epub 2007 Apr 5.
Diverse cholinergic signaling mechanisms regulate the excitability of striatal principal neurons and modulate striatal-dependent behavior. These effects are mediated, in part, by action at muscarinic receptors (mAChR), subtypes of which exhibit distinct patterns of expression across striatal neuronal populations. Non-selective mAChR blockade within the nucleus accumbens (NAc) has been shown to disrupt operant responding for food and to inhibit food consumption. However, the specific receptor subtypes mediating these effects are not known. Thus, we evaluated effects of intra-NAc infusions of pirenzepine and methoctramine, mAChR antagonisits with distinct binding affinity profiles, on operant responding for sucrose reward under a progressive ratio (PR) reinforcement schedule. Moderate to high doses of methoctramine disrupted operant responding and reduced behavioral breakpoint. In contrast, pirenzepine failed to impact operant performance at any dose tested. Methoctramine failed to affect latencies to complete appetitive-consummatory response sequences or to impact measures of acoustic startle, suggesting that its' disruptive effects on operant behavior were not consequent to gross motor impairment. Since methoctramine has a greater affinity for M(2) receptors compared to pirenzepine, which has a greater relative affinity for M(1) and M(3) receptors, these findings suggest that M(2) mAChRs within the NAc regulate behavioral processes underling the acquisition of reward.
多种胆碱能信号传导机制调节纹状体主要神经元的兴奋性，并调节依赖纹状体的行为。这些作用部分是通过作用于毒蕈碱受体（mAChR）介导的，其亚型在纹状体神经元群体中表现出不同的表达模式。伏隔核（NAc）内非选择性mAChR阻断已被证明会破坏对食物的操作性反应并抑制食物消耗。然而，介导这些作用的具体受体亚型尚不清楚。因此，我们评估了向NAc内注射哌仑西平和甲溴东莨菪碱（两种具有不同结合亲和力谱的mAChR拮抗剂）对渐进比率（PR）强化方案下蔗糖奖励操作性反应的影响。中高剂量的甲溴东莨菪碱破坏了操作性反应并降低了行为断点。相比之下，在任何测试剂量下，哌仑西平均未能影响操作性表现。甲溴东莨菪碱未能影响完成食欲性 consummatory 反应序列的潜伏期，也未影响听觉惊吓测量，这表明其对操作性行为的破坏作用并非源于严重的运动障碍。由于与对M(1)和M(3)受体具有更高相对亲和力的哌仑西平相比，甲溴东莨菪碱对M(2)受体具有更高的亲和力，这些发现表明NAc内的M(2) mAChRs调节奖励获取背后的行为过程。
