Neuroscience Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285-0510, USA.
Life Sci. 2011 Dec 5;89(23-24):862-7. doi: 10.1016/j.lfs.2011.09.014. Epub 2011 Sep 29.
Convergent data suggest that there is a hyperglutamatergic state that arises during relapse to drug seeking. Blockade of mGlu5 receptors provides one approach to dampening glutamate tone. However, the role of mGlu5 receptors in relapse to food seeking behavior has not been explored extensively and has not been scrutinized using receptor null mice.
Wild-type (WT) and mGlu5 receptor knockout (KO) mice were compared under the acquisition of a discriminated operant response maintained by food, during extinction of the response, and during the reinstatement of the response by food and food-associated stimuli. The impact of the mGlu5 receptor antagonist MTEP was investigated.
Acquisition and extinction were not markedly different in WT and KO mice. MTEP decreased response reinstatement in WT mice. This behavioral effect of MTEP was not present in the KO mice, demonstrating the dependence of the effect of MTEP on mGlu5 receptors. As with the effect of MTEP in WT mice, receptor deletion reduced response reinstatement in KO mice.
This is the first report to evaluate the reinstatement of food-seeking in mGlu5 receptor KO mice. The data reported here add to those in the literature that support a role for mGlu5 receptors in the control of this relapse effect. The data also reinforce the potential utility of mGlu5 receptor antagonists in relapse prevention to food-seeking behaviors.
汇聚的数据表明，在觅药行为复发期间会出现谷氨酸能亢进状态。阻断 mGlu5 受体是降低谷氨酸能音调的一种方法。然而，mGlu5 受体在觅食物行为复发中的作用尚未得到广泛探索，也未通过受体缺失小鼠进行深入研究。
在通过食物维持的辨别性操作性反应的获得、反应的消退以及食物和食物相关刺激引发的反应复燃期间，比较野生型（WT）和 mGlu5 受体敲除（KO）小鼠。研究了 mGlu5 受体拮抗剂 MTEP 的作用。
WT 和 KO 小鼠在获得和消退方面没有明显差异。MTEP 降低了 WT 小鼠的反应复燃。MTEP 在 KO 小鼠中没有这种行为效应，表明 MTEP 的作用依赖于 mGlu5 受体。与 MTEP 在 WT 小鼠中的作用一样，受体缺失也降低了 KO 小鼠的反应复燃。
这是首次评估 mGlu5 受体 KO 小鼠觅食物行为复燃的研究。这里报告的数据增加了文献中支持 mGlu5 受体在控制这种复发效应中的作用的证据。这些数据还加强了 mGlu5 受体拮抗剂在预防觅食物行为复发中的潜在效用。
