Alcohol Addiction- Metabotropic Glutamate Receptor Subtype 5 and its Ligands: How They All Come Together?

Title:Alcohol Addiction- Metabotropic Glutamate Receptor Subtype 5 and its Ligands: How They All Come Together?

Volume: 19 Issue: 8

Author(s): Jaya Kumar*, Zalina Ismail, Nurul Hazwani Hatta, Najwa Baharuddin, Hermizi Hapidin, Yvonne-Tee Get Bee, Ernie Yap and Rashidi Mohamed Pakri Mohamed

Affiliation:

• Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, 56000 Cheras, Kuala Lumpur,Malaysia

Keywords: Calmodulin, ethanol, homer, mGlu5, postsynaptic density proteins, alcohol addiction.

Abstract: In the past decade, many studies have highlighted the role of metabotropic glutamate receptor subtype 5 (mGlu5) modulators in attenuating alcohol-related biological effects such as alcohol consumption, alcohol-seeking and relapse-like behaviors. Taken together, these findings suggest that pharmacological agents acting at mGlu5 could be promising tools in curbing inebriation. mGlu5s are present abundantly in brain regions known to be involved in emotion regulation, motivation and drug administration. On a cellular level, they are primarily located at the postsynaptic part of the neuron where the receptor is functionally linked to various downstream proteins that are involved in cell signaling and gene transcription that mediate the alcohol-induced neuroplasticity. As well, the discovery of a functional link between mGlu5 and a specific isozyme, Protein Kinase C epsilon (PKCε) in mediating the attenuating effects of selective negative allosteric modulators of mGlu5 such as methyl- 6(phenylethynyl)pyridine (MPEP) and 3-((2-methyl-4-thiazolyl)ethynyl)pyridine (MTEP) has sparked interesting speculations. In this article, we shall review the following: the effects of acute and chronic alcohol intake on mGlu5 signaling; the effects of mGlu5 ligands on alcohol-related neurobehavioral changes that are currently being studied both at pre-clinical and clinical stages; and the mechanisms underlying the pharmacological effects of these drugs.

Cite this article as:

Kumar Jaya*, Ismail Zalina, Hatta Hazwani Nurul, Baharuddin Najwa , Hapidin Hermizi, Get Bee Yvonne-Tee, Yap Ernie and Pakri Mohamed Mohamed Rashidi , Alcohol Addiction- Metabotropic Glutamate Receptor Subtype 5 and its Ligands: How They All Come Together?, Current Drug Targets 2018; 19 (8) . https://dx.doi.org/10.2174/1389450118666170511144302