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

Kumar J, Hapidin H, Bee YT, Ismail Z - Behav Brain Funct (2013)

Bottom Line: MPEP at 10 mg/kg significantly attenuated ethanol withdrawal induced anxiety without any compromising effects on locomotor activities.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: BRAINetwork Centre for Neurocognitive Science, School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia. jaykumar5453@gmail.com.

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maze and the open field, low doses of MPEP (2.5, 5 mg/kg) significantly compromised the locomotor activities of ethanol withdrawn rats.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.

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The effect of MPEP on open and closed arm behaviours. The effect of MPEP (2.5, 5, 10, 20, and 30 mg/kg) on percent total time spent in the open arms (A), and the open and closed arm entries (B)of the automated elevated plus maze of ethanol withdrawn rats 7 hours after withdrawal. Each column represents the mean ± S.E.M [n = 8 for each group; EN = Control rats fed MLD without ethanol and treated with saline; EW = Ethanol Withdrawal (ethanol withdrawn group treated with normal saline); EW + 2.5, EW + 5,EW + 10, EW + 20, EW + 30 MPEP = ethanol withdrawn group treated with respective doses of MPEP (mg/kg);*p < 0.05,**P < 0.01, ***p < 0.001 vs EN; #p < 0.05, ##p < 0.01,###p < 0.001 vs EW; αp < 0.05, αααp < 0.001 vs 2.5 mg/kg MPEP; βββp < 0.001 vs 5 mg/kg MPEP; μμμp < 0.001 vs 20 mg/kg MPEP; $$p < 0.01 vs 30 mg/kg MPEP,One Way Analysis of Variance and post hoc Tukey’s test].
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Figure 2: The effect of MPEP on open and closed arm behaviours. The effect of MPEP (2.5, 5, 10, 20, and 30 mg/kg) on percent total time spent in the open arms (A), and the open and closed arm entries (B)of the automated elevated plus maze of ethanol withdrawn rats 7 hours after withdrawal. Each column represents the mean ± S.E.M [n = 8 for each group; EN = Control rats fed MLD without ethanol and treated with saline; EW = Ethanol Withdrawal (ethanol withdrawn group treated with normal saline); EW + 2.5, EW + 5,EW + 10, EW + 20, EW + 30 MPEP = ethanol withdrawn group treated with respective doses of MPEP (mg/kg);*p < 0.05,**P < 0.01, ***p < 0.001 vs EN; #p < 0.05, ##p < 0.01,###p < 0.001 vs EW; αp < 0.05, αααp < 0.001 vs 2.5 mg/kg MPEP; βββp < 0.001 vs 5 mg/kg MPEP; μμμp < 0.001 vs 20 mg/kg MPEP; $$p < 0.01 vs 30 mg/kg MPEP,One Way Analysis of Variance and post hoc Tukey’s test].

Mentions: Figure 2A illustrates a significant decrease in the total time spent in the open arms of the elevated plus maze in the ethanol withdrawn rats compared to rats fed MLD without ethanol [F(6,49) = 20.309; p < 0.0001]. The post Hoc analysis revealed a significant increase in the time spent in the open arms compared to the ethanol withdrawal group following administration of 2.5, 5, 10, 20, and 30 mg/kg MPEP. During ethanol withdrawal, rats treated with 5 and 10 mg/kg of MPEP spent significantly more time in the open arms of the elevated plus maze than rats treated with 2.5 mg/kg MPEP (Figure 2A).


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

Kumar J, Hapidin H, Bee YT, Ismail Z - Behav Brain Funct (2013)

The effect of MPEP on open and closed arm behaviours. The effect of MPEP (2.5, 5, 10, 20, and 30 mg/kg) on percent total time spent in the open arms (A), and the open and closed arm entries (B)of the automated elevated plus maze of ethanol withdrawn rats 7 hours after withdrawal. Each column represents the mean ± S.E.M [n = 8 for each group; EN = Control rats fed MLD without ethanol and treated with saline; EW = Ethanol Withdrawal (ethanol withdrawn group treated with normal saline); EW + 2.5, EW + 5,EW + 10, EW + 20, EW + 30 MPEP = ethanol withdrawn group treated with respective doses of MPEP (mg/kg);*p < 0.05,**P < 0.01, ***p < 0.001 vs EN; #p < 0.05, ##p < 0.01,###p < 0.001 vs EW; αp < 0.05, αααp < 0.001 vs 2.5 mg/kg MPEP; βββp < 0.001 vs 5 mg/kg MPEP; μμμp < 0.001 vs 20 mg/kg MPEP; $$p < 0.01 vs 30 mg/kg MPEP,One Way Analysis of Variance and post hoc Tukey’s test].
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Figure 2: The effect of MPEP on open and closed arm behaviours. The effect of MPEP (2.5, 5, 10, 20, and 30 mg/kg) on percent total time spent in the open arms (A), and the open and closed arm entries (B)of the automated elevated plus maze of ethanol withdrawn rats 7 hours after withdrawal. Each column represents the mean ± S.E.M [n = 8 for each group; EN = Control rats fed MLD without ethanol and treated with saline; EW = Ethanol Withdrawal (ethanol withdrawn group treated with normal saline); EW + 2.5, EW + 5,EW + 10, EW + 20, EW + 30 MPEP = ethanol withdrawn group treated with respective doses of MPEP (mg/kg);*p < 0.05,**P < 0.01, ***p < 0.001 vs EN; #p < 0.05, ##p < 0.01,###p < 0.001 vs EW; αp < 0.05, αααp < 0.001 vs 2.5 mg/kg MPEP; βββp < 0.001 vs 5 mg/kg MPEP; μμμp < 0.001 vs 20 mg/kg MPEP; $$p < 0.01 vs 30 mg/kg MPEP,One Way Analysis of Variance and post hoc Tukey’s test].
Mentions: Figure 2A illustrates a significant decrease in the total time spent in the open arms of the elevated plus maze in the ethanol withdrawn rats compared to rats fed MLD without ethanol [F(6,49) = 20.309; p < 0.0001]. The post Hoc analysis revealed a significant increase in the time spent in the open arms compared to the ethanol withdrawal group following administration of 2.5, 5, 10, 20, and 30 mg/kg MPEP. During ethanol withdrawal, rats treated with 5 and 10 mg/kg of MPEP spent significantly more time in the open arms of the elevated plus maze than rats treated with 2.5 mg/kg MPEP (Figure 2A).

Bottom Line: MPEP at 10 mg/kg significantly attenuated ethanol withdrawal induced anxiety without any compromising effects on locomotor activities.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: BRAINetwork Centre for Neurocognitive Science, School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia. jaykumar5453@gmail.com.

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.

Show MeSH
Related in: MedlinePlus