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The phosphodiesterase-4 inhibitor roflumilast decreases ethanol consumption in C57BL/6J mice

Rationale Alcohol use disorders have become one of the most damaging psychiatric disorders in the world; however, there are no ideal treatments in clinic. Phosphodiesterase-4 (PDE4), an enzyme that specifically hydrolyzes intracellular cyclic AMP (cAMP), has been involved in alcohol use disorders. R... Full description

Journal Title: Psychopharmacology 2017-05-06, Vol.234 (16), p.2409-2419
Main Author: Liu, Xin
Other Authors: Hao, Pi-Da , Yang, Ming-Feng , Sun, Jing-Yi , Mao, Lei-Lei , Fan, Cun-Dong , Zhang, Zong-Yong , Li, Da-Wei , Yang, Xiao-Yi , Sun, Bao-Liang , Zhang, Han-Ting
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: Berlin/Heidelberg: Springer Berlin Heidelberg
ID: ISSN: 0033-3158
Link: https://www.ncbi.nlm.nih.gov/pubmed/28477089
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recordid: cdi_proquest_miscellaneous_1896037381
title: The phosphodiesterase-4 inhibitor roflumilast decreases ethanol consumption in C57BL/6J mice
format: Article
creator:
  • Liu, Xin
  • Hao, Pi-Da
  • Yang, Ming-Feng
  • Sun, Jing-Yi
  • Mao, Lei-Lei
  • Fan, Cun-Dong
  • Zhang, Zong-Yong
  • Li, Da-Wei
  • Yang, Xiao-Yi
  • Sun, Bao-Liang
  • Zhang, Han-Ting
subjects:
  • Alcohol Drinking
  • Alcohol use
  • Alcoholic beverages
  • Alcoholism
  • Aminopyridines - pharmacology
  • Animals
  • Benzamides - pharmacology
  • Biomedical and Life Sciences
  • Biomedicine
  • Cyclic AMP
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Cyclopropanes - pharmacology
  • Disorders
  • Dosage and administration
  • Drinking behavior
  • Drug therapy
  • Enzymes
  • Ethanol
  • Ethanol - administration & dosage
  • Inhibitor drugs
  • Locomotor activity
  • Lung diseases
  • Male
  • Mental disorders
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity - drug effects
  • Neurosciences
  • Obstructive lung disease
  • Original Investigation
  • Patient outcomes
  • Pharmacology/Toxicology
  • Phosphodiesterase
  • Phosphodiesterase 4 Inhibitors - pharmacology
  • Psychiatry
  • Psychopharmacology
  • Quinine
  • Reinforcement
  • Rodents
  • Roflumilast
  • Rolipram
  • Rolipram - pharmacology
  • Sucrose
  • Sugars
ispartof: Psychopharmacology, 2017-05-06, Vol.234 (16), p.2409-2419
description: Rationale Alcohol use disorders have become one of the most damaging psychiatric disorders in the world; however, there are no ideal treatments in clinic. Phosphodiesterase-4 (PDE4), an enzyme that specifically hydrolyzes intracellular cyclic AMP (cAMP), has been involved in alcohol use disorders. Roflumilast is the first PDE4 inhibitor approved for treatment of chronic obstructive pulmonary diseases in clinic. It was of particular interest to researchers to determine whether roflumilast altered ethanol consumption. Objectives The present study tried to determine the effects of roflumilast on ethanol intake and preference. Methods We used the two-bottle choice paradigm to assess ethanol intake and preference in C57BL/6J mice treated with roflumilast (1, 3, or 10 mg/kg) or rolipram (0.5 mg/kg; positive control). The effect of roflumilast was verified using the ethanol drinking-in-dark (DID) test. Locomotor activity was examined using the open-field test. Intake of sucrose or quinine was also tested to determine whether natural reward preference and aversive stimuli were involved in the effect of PDE4 inhibitors. Results Similar to rolipram, roflumilast decreased ethanol intake and preference in two-bottle choice and DID tests in a dose-dependent manner, with significant changes at the dose of 10 mg/kg; in contrast, roflumilast did not affect sucrose or quinine drinking, although it decreased locomotor activity at the high dose within 3 h of treatment. Conclusions These data provide novel demonstration for the effect of roflumilast on ethanol consumption and suggest that roflumilast may be beneficial for treatment of alcoholism.
language: eng
source:
identifier: ISSN: 0033-3158
fulltext: no_fulltext
issn:
  • 0033-3158
  • 1432-2072
url: Link


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titleThe phosphodiesterase-4 inhibitor roflumilast decreases ethanol consumption in C57BL/6J mice
creatorLiu, Xin ; Hao, Pi-Da ; Yang, Ming-Feng ; Sun, Jing-Yi ; Mao, Lei-Lei ; Fan, Cun-Dong ; Zhang, Zong-Yong ; Li, Da-Wei ; Yang, Xiao-Yi ; Sun, Bao-Liang ; Zhang, Han-Ting
creatorcontribLiu, Xin ; Hao, Pi-Da ; Yang, Ming-Feng ; Sun, Jing-Yi ; Mao, Lei-Lei ; Fan, Cun-Dong ; Zhang, Zong-Yong ; Li, Da-Wei ; Yang, Xiao-Yi ; Sun, Bao-Liang ; Zhang, Han-Ting
descriptionRationale Alcohol use disorders have become one of the most damaging psychiatric disorders in the world; however, there are no ideal treatments in clinic. Phosphodiesterase-4 (PDE4), an enzyme that specifically hydrolyzes intracellular cyclic AMP (cAMP), has been involved in alcohol use disorders. Roflumilast is the first PDE4 inhibitor approved for treatment of chronic obstructive pulmonary diseases in clinic. It was of particular interest to researchers to determine whether roflumilast altered ethanol consumption. Objectives The present study tried to determine the effects of roflumilast on ethanol intake and preference. Methods We used the two-bottle choice paradigm to assess ethanol intake and preference in C57BL/6J mice treated with roflumilast (1, 3, or 10 mg/kg) or rolipram (0.5 mg/kg; positive control). The effect of roflumilast was verified using the ethanol drinking-in-dark (DID) test. Locomotor activity was examined using the open-field test. Intake of sucrose or quinine was also tested to determine whether natural reward preference and aversive stimuli were involved in the effect of PDE4 inhibitors. Results Similar to rolipram, roflumilast decreased ethanol intake and preference in two-bottle choice and DID tests in a dose-dependent manner, with significant changes at the dose of 10 mg/kg; in contrast, roflumilast did not affect sucrose or quinine drinking, although it decreased locomotor activity at the high dose within 3 h of treatment. Conclusions These data provide novel demonstration for the effect of roflumilast on ethanol consumption and suggest that roflumilast may be beneficial for treatment of alcoholism.
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subjectAlcohol Drinking ; Alcohol use ; Alcoholic beverages ; Alcoholism ; Aminopyridines - pharmacology ; Animals ; Benzamides - pharmacology ; Biomedical and Life Sciences ; Biomedicine ; Cyclic AMP ; Cyclic Nucleotide Phosphodiesterases, Type 4 ; Cyclopropanes - pharmacology ; Disorders ; Dosage and administration ; Drinking behavior ; Drug therapy ; Enzymes ; Ethanol ; Ethanol - administration & dosage ; Inhibitor drugs ; Locomotor activity ; Lung diseases ; Male ; Mental disorders ; Mice ; Mice, Inbred C57BL ; Motor Activity - drug effects ; Neurosciences ; Obstructive lung disease ; Original Investigation ; Patient outcomes ; Pharmacology/Toxicology ; Phosphodiesterase ; Phosphodiesterase 4 Inhibitors - pharmacology ; Psychiatry ; Psychopharmacology ; Quinine ; Reinforcement ; Rodents ; Roflumilast ; Rolipram ; Rolipram - pharmacology ; Sucrose ; Sugars
ispartofPsychopharmacology, 2017-05-06, Vol.234 (16), p.2409-2419
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descriptionRationale Alcohol use disorders have become one of the most damaging psychiatric disorders in the world; however, there are no ideal treatments in clinic. Phosphodiesterase-4 (PDE4), an enzyme that specifically hydrolyzes intracellular cyclic AMP (cAMP), has been involved in alcohol use disorders. Roflumilast is the first PDE4 inhibitor approved for treatment of chronic obstructive pulmonary diseases in clinic. It was of particular interest to researchers to determine whether roflumilast altered ethanol consumption. Objectives The present study tried to determine the effects of roflumilast on ethanol intake and preference. Methods We used the two-bottle choice paradigm to assess ethanol intake and preference in C57BL/6J mice treated with roflumilast (1, 3, or 10 mg/kg) or rolipram (0.5 mg/kg; positive control). The effect of roflumilast was verified using the ethanol drinking-in-dark (DID) test. Locomotor activity was examined using the open-field test. Intake of sucrose or quinine was also tested to determine whether natural reward preference and aversive stimuli were involved in the effect of PDE4 inhibitors. Results Similar to rolipram, roflumilast decreased ethanol intake and preference in two-bottle choice and DID tests in a dose-dependent manner, with significant changes at the dose of 10 mg/kg; in contrast, roflumilast did not affect sucrose or quinine drinking, although it decreased locomotor activity at the high dose within 3 h of treatment. Conclusions These data provide novel demonstration for the effect of roflumilast on ethanol consumption and suggest that roflumilast may be beneficial for treatment of alcoholism.
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18Ethanol - administration & dosage
19Inhibitor drugs
20Locomotor activity
21Lung diseases
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26Motor Activity - drug effects
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titleThe phosphodiesterase-4 inhibitor roflumilast decreases ethanol consumption in C57BL/6J mice
authorLiu, Xin ; Hao, Pi-Da ; Yang, Ming-Feng ; Sun, Jing-Yi ; Mao, Lei-Lei ; Fan, Cun-Dong ; Zhang, Zong-Yong ; Li, Da-Wei ; Yang, Xiao-Yi ; Sun, Bao-Liang ; Zhang, Han-Ting
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6Benzamides - pharmacology
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37Reinforcement
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39Roflumilast
40Rolipram
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42Sucrose
43Sugars
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2Yang, Ming-Feng
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abstractRationale Alcohol use disorders have become one of the most damaging psychiatric disorders in the world; however, there are no ideal treatments in clinic. Phosphodiesterase-4 (PDE4), an enzyme that specifically hydrolyzes intracellular cyclic AMP (cAMP), has been involved in alcohol use disorders. Roflumilast is the first PDE4 inhibitor approved for treatment of chronic obstructive pulmonary diseases in clinic. It was of particular interest to researchers to determine whether roflumilast altered ethanol consumption. Objectives The present study tried to determine the effects of roflumilast on ethanol intake and preference. Methods We used the two-bottle choice paradigm to assess ethanol intake and preference in C57BL/6J mice treated with roflumilast (1, 3, or 10 mg/kg) or rolipram (0.5 mg/kg; positive control). The effect of roflumilast was verified using the ethanol drinking-in-dark (DID) test. Locomotor activity was examined using the open-field test. Intake of sucrose or quinine was also tested to determine whether natural reward preference and aversive stimuli were involved in the effect of PDE4 inhibitors. Results Similar to rolipram, roflumilast decreased ethanol intake and preference in two-bottle choice and DID tests in a dose-dependent manner, with significant changes at the dose of 10 mg/kg; in contrast, roflumilast did not affect sucrose or quinine drinking, although it decreased locomotor activity at the high dose within 3 h of treatment. Conclusions These data provide novel demonstration for the effect of roflumilast on ethanol consumption and suggest that roflumilast may be beneficial for treatment of alcoholism.
copBerlin/Heidelberg
pubSpringer Berlin Heidelberg
pmid28477089
doi10.1007/s00213-017-4631-8