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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maze and the open field, low doses of MPEP (2.5, 5 mg/kg) significantly compromised the locomotor activities of ethanol withdrawn rats.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 locomotion of ethanol naïve rats. The effect of MPEP (2.5, 5, 10, 20, and 30 mg/kg) on basic and fine movement (A), X and Y ambulation (B) in automated elevated plus maze of ethanol naïve rats. Each column represents the mean ± S.E.M [n = 8 for each group; EN = Control rats fed MLD without ethanol and treated with saline; EN + 2.5,EN + 5,EN + 10, EN + 20, EN + 30MPEP = ethanol naive group treated with respective doses of MPEP (mg/kg); One Way Analysis of Variance].
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Figure 3: The effect of MPEP on locomotion of ethanol naïve rats. The effect of MPEP (2.5, 5, 10, 20, and 30 mg/kg) on basic and fine movement (A), X and Y ambulation (B) in automated elevated plus maze of ethanol naïve rats. Each column represents the mean ± S.E.M [n = 8 for each group; EN = Control rats fed MLD without ethanol and treated with saline; EN + 2.5,EN + 5,EN + 10, EN + 20, EN + 30MPEP = ethanol naive group treated with respective doses of MPEP (mg/kg); One Way Analysis of Variance].

Mentions: Figure 3A shows the effect of MPEP (2.5, 5, 10, 20, 30 mg/kg) on the basic movement of ethanol naïve rats. Neither doses of MPEP produced any significant effect on the basic movement of the ethanol naïve rats [F(5,42) = 0.892; p > 0.05] (Figure 3A). Likewise, MPEP (2.5, 5, 10, 20, 30 mg/kg) had no significant effect on the fine movement of ethanol naïve rats [F(5,42) = 1.767; p > 0.05] (Figure 3A).


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 locomotion of ethanol naïve rats. The effect of MPEP (2.5, 5, 10, 20, and 30 mg/kg) on basic and fine movement (A), X and Y ambulation (B) in automated elevated plus maze of ethanol naïve rats. Each column represents the mean ± S.E.M [n = 8 for each group; EN = Control rats fed MLD without ethanol and treated with saline; EN + 2.5,EN + 5,EN + 10, EN + 20, EN + 30MPEP = ethanol naive group treated with respective doses of MPEP (mg/kg); One Way Analysis of Variance].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4222772&req=5

Figure 3: The effect of MPEP on locomotion of ethanol naïve rats. The effect of MPEP (2.5, 5, 10, 20, and 30 mg/kg) on basic and fine movement (A), X and Y ambulation (B) in automated elevated plus maze of ethanol naïve rats. Each column represents the mean ± S.E.M [n = 8 for each group; EN = Control rats fed MLD without ethanol and treated with saline; EN + 2.5,EN + 5,EN + 10, EN + 20, EN + 30MPEP = ethanol naive group treated with respective doses of MPEP (mg/kg); One Way Analysis of Variance].
Mentions: Figure 3A shows the effect of MPEP (2.5, 5, 10, 20, 30 mg/kg) on the basic movement of ethanol naïve rats. Neither doses of MPEP produced any significant effect on the basic movement of the ethanol naïve rats [F(5,42) = 0.892; p > 0.05] (Figure 3A). Likewise, MPEP (2.5, 5, 10, 20, 30 mg/kg) had no significant effect on the fine movement of ethanol naïve rats [F(5,42) = 1.767; p > 0.05] (Figure 3A).

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