Pharmacological activation of mGlu4 and mGlu7 receptors, by LSP2-9166, reduces ethanol consumption and relapse in rat

Pharmacological activation of mGlu4 and mGlu7 receptors, by LSP2-9166, reduces ethanol... Addiction is a chronic and highly relapsing disorder hypothesized to be produced by an imbalance between excitatory and inhibitory neurotransmission. For more than a decade, emerging evidence indicates that manipulation of glutamatergic neurotransmission, by group III mGlu receptors (mGlu4/7/8), could be a promising approach to develop therapeutic agents for the treatment of addiction. Thus, the aim of the present study is to determine whether LSP2-9166, a mixed mGlu4/mGlu7 orthosteric agonist, could reduce ethanol self-administration, ethanol motivation and reacquisition after protracted abstinence in a preclinical model of excessive ethanol intake. Male Long Evans rats were chronically trained to consume large amount of ethanol in operant cages for several weeks. Once they reached a stable level of consumption (about 1 g of pure ethanol/kg bodyweight/15min), the effect of LSP2-9166 was evaluated on different aspects of the operant self-administration behavior. In this study, we found that the intracerebroventricular infusion of LSP2-9166 dose dependently reduced ethanol consumption, motivation for ethanol and reacquisition of ethanol self-administration after abstinence. Together, these results support recent preclinical findings showing that pharmacological modulation of mGlu receptors may serve as an effective treatment for reducing ethanol consumption and relapse. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neuropharmacology Elsevier

Pharmacological activation of mGlu4 and mGlu7 receptors, by LSP2-9166, reduces ethanol consumption and relapse in rat

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Publisher
Elsevier
Copyright
Copyright © 2018 Elsevier Ltd
ISSN
0028-3908
eISSN
1873-7064
D.O.I.
10.1016/j.neuropharm.2018.01.031
Publisher site
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Abstract

Addiction is a chronic and highly relapsing disorder hypothesized to be produced by an imbalance between excitatory and inhibitory neurotransmission. For more than a decade, emerging evidence indicates that manipulation of glutamatergic neurotransmission, by group III mGlu receptors (mGlu4/7/8), could be a promising approach to develop therapeutic agents for the treatment of addiction. Thus, the aim of the present study is to determine whether LSP2-9166, a mixed mGlu4/mGlu7 orthosteric agonist, could reduce ethanol self-administration, ethanol motivation and reacquisition after protracted abstinence in a preclinical model of excessive ethanol intake. Male Long Evans rats were chronically trained to consume large amount of ethanol in operant cages for several weeks. Once they reached a stable level of consumption (about 1 g of pure ethanol/kg bodyweight/15min), the effect of LSP2-9166 was evaluated on different aspects of the operant self-administration behavior. In this study, we found that the intracerebroventricular infusion of LSP2-9166 dose dependently reduced ethanol consumption, motivation for ethanol and reacquisition of ethanol self-administration after abstinence. Together, these results support recent preclinical findings showing that pharmacological modulation of mGlu receptors may serve as an effective treatment for reducing ethanol consumption and relapse.

Journal

NeuropharmacologyElsevier

Published: May 1, 2018

References

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