: Metabotropic glutamate subtype 5 (mGlu5) receptors are implicated in various forms of synaptic plasticity, including drugs of abuse. In drug-addicted individuals, associative memories can drive relapse to drug use. The present study investigated the potential of the mGlu5 receptor positive allosteric modulator (PAM), VU-29 (30 mg/kg, i.p.), to inhibit the maintenance of a learned association between ethanol and environmental context by using conditioned place preference (CPP) in rats. The ethanol-CPP was established by the administration of ethanol (1.0 g/kg, i.p. × 10 days) using an unbiased procedure. Following ethanol conditioning, VU-29 was administered at various post-conditioning times (ethanol free state at the home cage) to ascertain if there was a temporal window during which VU-29 would be effective. Our experiments indicated that VU-29 did not affect the expression of ethanol-induced CPP when it was given over two post-conditioning days. However, the expression of ethanol-CPP was inhibited by 10-day home cage administration of VU-29, but not by first 2-day or last 2-day injection of VU-29 during the 10-day period. These findings reveal that VU-29 can inhibit the maintenance of ethanol-induced CPP, and that treatment duration contributes to this effect of VU-29. Furthermore, VU-29 effect was reversed by pretreatment with either MTEP (the mGlu5 receptor antagonist), or MK-801 (the N-methyl-D-aspartate-NMDA receptor antagonist). Thus, the inhibitory effect of VU-29 is dependent on the functional interaction between mGlu5 and NMDA receptors. Because a reduction in ethanol-associated cues can reduce relapse, mGlu5 receptor PAM would be useful for therapy of alcoholism. Future research is required to confirm the current findings.

中文翻译：

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代谢型谷氨酸受体5（VU-29）的正变构调节剂对环境提示与乙醇奖励特性之间维持关联的影响。

：代谢型谷氨酸亚型5（mGlu5）受体涉及各种形式的突触可塑性，包括滥用药物。在吸毒成瘾的个体中，联想记忆会促使吸毒复发。本研究调查了mGlu5受体阳性变构调节剂（PAM）VU-29（30 mg / kg，ip）通过使用条件性位置偏爱（CPP）来抑制维持乙醇与环境之间的学习关联的潜力在大鼠中。乙醇-CPP是通过使用无偏规程给予乙醇（1.0 g / kg，腹膜内×10天）建立的。乙醇调理后，在各种后调理时间（家笼中无乙醇状态）施用VU-29，以确定在VU-29有效期间是否存在时间窗。我们的实验表明，在调理后两天内给予VU-29不会影响乙醇诱导的CPP的表达。然而，乙醇-CPP的表达被VU-29的10天家庭笼给药所抑制，但在10天的时间内最初2天或最后2天注射VU-29并没有受到抑制。这些发现表明，VU-29可以抑制乙醇诱导的CPP的维持，并且治疗持续时间有助于VU-29的这种作用。此外，通过用MTEP（mGlu5受体拮抗剂）或MK-801（N-甲基-D-天冬氨酸-NMDA受体拮抗剂）进行预处理可以逆转VU-29的作用。因此，VU-29的抑制作用取决于mGlu5和NMDA受体之间的功能相互作用。由于减少与乙醇相关的提示可以减少复发，mGlu5受体PAM可用于治疗酒精中毒。需要进一步的研究以确认当前的发现。