Effects of the mGluR5 antagonist MPEP on ethanol withdrawal induced anxiety-like syndrome in rats

Murthy Jaya Kumar, Hermizi Hapidin, Yvonne Tee G Bee, Zalina Ismail

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Abstinence from chronic ethanol consumption leads to the manifestation of a variety of symptoms attributed to central nervous system hyperexcitability, such as increased irritability, anxiety, and restlessness. Recent studies have demonstrated the importance of metabotropic glutamate receptor 5 (mGluR5) in addictive behaviours. This study investigates the effects of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) on ethanol withdrawal induced anxiety using two behavioural paradigms. Male Wistar rats were fed a Modified Liquid Diet (MLD) containing low fat cow milk, sucrose, and maltodextrin with a gradual introduction of 2.4%, 4.8% and 7.2% ethanol for 20 days. Six hours into ethanol withdrawal, the rats were intraperitoneally injected with normal saline and MPEP (2.5, 5.0, 10, 20, 30 mg/kg) and were assessed for ethanol withdrawal induced anxiety-like syndrome using an automated elevated plus maze and an open field. MPEP at 10 mg/kg significantly attenuated ethanol withdrawal induced anxiety without any compromising effects on locomotor activities. Despite reversing several indices of ethanol withdrawal induced anxiety in both the elevated plus maze and the open field, low doses of MPEP (2.5, 5 mg/kg) significantly compromised the locomotor activities of ethanol withdrawn rats. High doses of MPEP (20 and 30 mg/kg) significantly attenuated withdrawal anxiety when tested in the elevated plus maze but not in the open field. Administration of MPEP (2.5, 5, 10, 20, 30 mg/kg) has no significant compromising effect on the locomotor activities of ethanol naïve rats. Despite significantly reducing withdrawal anxiety in both behavioural paradigms at 10 mg/kg, the compromising effects of low and high doses of MPEP must be further explored along with the therapeutic efficiency of this drug for relieving withdrawal induced anxiety.

Original languageEnglish
Article number43
JournalBehavioral and Brain Functions
Volume9
Issue number1
DOIs
Publication statusPublished - 26 Nov 2013
Externally publishedYes

Fingerprint

Excitatory Amino Acid Antagonists
Metabotropic Glutamate Receptors
Ethanol
Anxiety
Locomotion
Metabotropic Glutamate 5 Receptor
Addictive Behavior
pyridine
Psychomotor Agitation
Fat-Restricted Diet
Sucrose
Wistar Rats
Milk
Central Nervous System

Keywords

  • Ethanol withdrawal induced anxiety
  • mGluR5
  • MPEP

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Biological Psychiatry
  • Cognitive Neuroscience

Cite this

Effects of the mGluR5 antagonist MPEP on ethanol withdrawal induced anxiety-like syndrome in rats. / Jaya Kumar, Murthy; Hapidin, Hermizi; Bee, Yvonne Tee G; Ismail, Zalina.

In: Behavioral and Brain Functions, Vol. 9, No. 1, 43, 26.11.2013.

Research output: Contribution to journalArticle

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