Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
PLoS One. 2010 Nov 30;5(11):e15085. doi: 10.1371/journal.pone.0015085.
Pharmacological and genetic studies have suggested that the metabotropic glutamate receptor 5 (mGluR5) is critically involved in mediating the reinforcing effects of drugs of abuse, but not food. The purpose of this study was to use mGluR5 knockout (KO), heterozygous (Het), and wildtype (WT) mice to determine if mGluR5 modulates operant sensation seeking (OSS), an operant task that uses varied sensory stimuli as a reinforcer. We found that mGluR5 KO mice had significantly reduced OSS responding relative to WT mice, while Het mice displayed a paradoxical increase in OSS responding. Neither KO nor Het mice exhibited altered operant responding for food as a reinforcer. Further, we assessed mGluR5 KO, Het and WT mice across a battery of cocaine locomotor, place preference and anxiety related tests. Although KO mice showed expected differences in some locomotor and anxiety measures, Het mice either exhibited no phenotype or an intermediate one. In total, these data demonstrate a key role for mGluR5 in OSS, indicating an important role for this receptor in reinforcement-based behavior.
药理学和遗传学研究表明，代谢型谷氨酸受体 5（mGluR5）在介导滥用药物的强化作用中起着关键作用，但对食物没有作用。本研究的目的是使用 mGluR5 敲除（KO）、杂合（Het）和野生型（WT）小鼠来确定 mGluR5 是否调节操作性感觉寻求（OSS），这是一种使用不同感觉刺激作为强化物的操作性任务。我们发现，mGluR5 KO 小鼠的 OSS 反应明显低于 WT 小鼠，而 Het 小鼠的 OSS 反应则出现反常增加。KO 或 Het 小鼠均未表现出食物作为强化物的操作性反应改变。此外，我们在一系列可卡因运动、位置偏好和焦虑相关测试中评估了 mGluR5 KO、Het 和 WT 小鼠。尽管 KO 小鼠在一些运动和焦虑测量中表现出预期的差异，但 Het 小鼠要么没有表现出表型，要么表现出中间型。总的来说，这些数据表明 mGluR5 在 OSS 中起着关键作用，表明该受体在基于强化的行为中起着重要作用。
