Abstract
Glutamate is essential for learning and memory processes, and acute and chronic exposures to ethanol (or protracted abstinence) alter glutamatergic transmission. In the current study, we investigated the effects of VU-29, positive allosteric modulator of metabotropic glutamate 5 (mGlu5) receptor, on the acute ethanol- and ethanol withdrawal-induced impairment of novel object recognition (NOR) task in rats. The influence of VU-29 (30 mg/kg) on memory retrieval was measured (a) at 4-h delay after acute ethanol administration, as well as (b) after acute withdrawal (24 and 48 h) of repeated (2.0 g/kg, once daily for 7 days) ethanol administration. Additionally, the effects of VU-29 on expression of mGlu5 and mGlu2 receptor proteins in the hippocampus, prefrontal cortex, and striatum were determined 48 h after ethanol withdrawal. Our results indicated that VU-29, given before acute ethanol administration, prevented the ethanol-induced impairments in spatial memory retrieval. Furthermore, VU-29 given before the testing session on the first day of abstinence facilitated NOR performance in ethanol-withdrawn rats at 4- and 24-h delay after administration. Our ELISA results show that VU-29 normalized ethanol withdrawal induced increase in expression of mGlu5 receptor protein in the hippocampus, prefrontal cortex, and striatum, as well as expression of mGlu2 receptor protein in the hippocampus. Thus, results from our study indicate that positive modulation of mGlu5 receptor prevented and reversed ethanol-induced memory impairment. Moreover, mGlu5 (hippocampus, prefrontal cortex, and striatum) and mGlu2 (hippocampus) receptors play an important role in the ethanol-induced recognition memory impairment induced by ethanol withdrawal.
Highlights
Acute ethanol intoxication (Ryabinin 1998; White et al 2000) and long-term ethanol consumption (MeyerhoffRecognition memory is the ability to recognize previously encountered events, objects, or people, and this memory depends on the integrity of the medial temporal lobe regionsNeurotox Res (2018) 33:607–620(Squire et al 2007), which include the hippocampus and perirhinal cortex (Squire and Zola-Morgan 1991)
It has been indicated that some forms of recognition memory recruit the medial prefrontal cortex (Bekinschtein and Weisstaub 2014; Morici et al 2015) that is associated with successful retrieval of the object recognition task (Bekinschtein and Weisstaub 2014; Morici et al 2015)
We examined the influence of the metabotropic glutamate 5 (mGlu5) receptor-positive allosteric modulator, VU-29, on ethanol-induced impairment of recognition, in rats, using the novel object recognition (NOR) test
Summary
Acute ethanol intoxication (Ryabinin 1998; White et al 2000) and long-term ethanol consumption (MeyerhoffRecognition memory is the ability to recognize previously encountered events, objects, or people, and this memory depends on the integrity of the medial temporal lobe regionsNeurotox Res (2018) 33:607–620(Squire et al 2007), which include the hippocampus and perirhinal cortex (Squire and Zola-Morgan 1991). It has been recently reported that metabotropic glutamate subtype 5 (mGlu5) receptor-dependent signaling, preferentially in limbic structures, is involved in cognition (e.g. memory and learning), novelty seeking behavior, and compulsivity. These factors are core personality traits increasing the susceptibility to drug addiction (Leurquin-Sterk et al 2015). Preclinical researches suggest the important role of this receptor in ethanol drinking (Cozzoli et al 2009, 2012; Besheer et al 2010; Sinclair et al 2012) and in the memory formation responsible for the chronic relapsing nature of alcohol abuse (Obara et al 2009). This receptor is a candidate target for the treatment of addictive disorders (Mihov and Hasler 2016)
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