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The phosphodiesterase-4 inhibitor roflumilast decreases ethanol consumption in C57BL/6J mice.
Psychopharmacology (Berl). 2017 Aug; 234(16):2409-2419.P

Abstract

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.

Authors+Show Affiliations

Key Lab of Cerebral Microcirculation in Universities of Shandong, Institute of Neurological Disorders, Taishan Medical University, Taian, Shandong, 271000, China. Institute of Pharmacology, Taishan Medical University, Taian, Shandong, 271016, China. Department of Medical Psychology, School of Basic Medical Sciences, Taishan Medical University, Taian, Shandong, 271000, China.Key Lab of Cerebral Microcirculation in Universities of Shandong, Institute of Neurological Disorders, Taishan Medical University, Taian, Shandong, 271000, China.Key Lab of Cerebral Microcirculation in Universities of Shandong, Institute of Neurological Disorders, Taishan Medical University, Taian, Shandong, 271000, China.Key Lab of Cerebral Microcirculation in Universities of Shandong, Institute of Neurological Disorders, Taishan Medical University, Taian, Shandong, 271000, China.Key Lab of Cerebral Microcirculation in Universities of Shandong, Institute of Neurological Disorders, Taishan Medical University, Taian, Shandong, 271000, China.Key Lab of Cerebral Microcirculation in Universities of Shandong, Institute of Neurological Disorders, Taishan Medical University, Taian, Shandong, 271000, China.Key Lab of Cerebral Microcirculation in Universities of Shandong, Institute of Neurological Disorders, Taishan Medical University, Taian, Shandong, 271000, China.Key Lab of Cerebral Microcirculation in Universities of Shandong, Institute of Neurological Disorders, Taishan Medical University, Taian, Shandong, 271000, China.Key Lab of Cerebral Microcirculation in Universities of Shandong, Institute of Neurological Disorders, Taishan Medical University, Taian, Shandong, 271000, China. xyyang@tsmc.edu.cn.Key Lab of Cerebral Microcirculation in Universities of Shandong, Institute of Neurological Disorders, Taishan Medical University, Taian, Shandong, 271000, China. blsun@tsmc.edu.cn. Department of Neurology, Affiliated Hospital, Taishan Medical University, Taian, Shandong, 271000, China. blsun@tsmc.edu.cn.Institute of Pharmacology, Taishan Medical University, Taian, Shandong, 271016, China. hzhang@hsc.wvu.edu. Departments of Behavioral Medicine & Psychiatry and Physiology & Pharmacology, Blanchette Rockefeller Neurosciences Institute, West Virginia University Health Sciences Center, Morgantown, WV, 26506, USA. hzhang@hsc.wvu.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28477089

Citation

Liu, Xin, et al. "The Phosphodiesterase-4 Inhibitor Roflumilast Decreases Ethanol Consumption in C57BL/6J Mice." Psychopharmacology, vol. 234, no. 16, 2017, pp. 2409-2419.
Liu X, Hao PD, Yang MF, et al. The phosphodiesterase-4 inhibitor roflumilast decreases ethanol consumption in C57BL/6J mice. Psychopharmacology (Berl). 2017;234(16):2409-2419.
Liu, X., Hao, P. D., Yang, M. F., Sun, J. Y., Mao, L. L., Fan, C. D., Zhang, Z. Y., Li, D. W., Yang, X. Y., Sun, B. L., & Zhang, H. T. (2017). The phosphodiesterase-4 inhibitor roflumilast decreases ethanol consumption in C57BL/6J mice. Psychopharmacology, 234(16), 2409-2419. https://doi.org/10.1007/s00213-017-4631-8
Liu X, et al. The Phosphodiesterase-4 Inhibitor Roflumilast Decreases Ethanol Consumption in C57BL/6J Mice. Psychopharmacology (Berl). 2017;234(16):2409-2419. PubMed PMID: 28477089.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The phosphodiesterase-4 inhibitor roflumilast decreases ethanol consumption in C57BL/6J mice. AU - Liu,Xin, AU - Hao,Pi-Da, AU - Yang,Ming-Feng, AU - Sun,Jing-Yi, AU - Mao,Lei-Lei, AU - Fan,Cun-Dong, AU - Zhang,Zong-Yong, AU - Li,Da-Wei, AU - Yang,Xiao-Yi, AU - Sun,Bao-Liang, AU - Zhang,Han-Ting, Y1 - 2017/05/06/ PY - 2016/07/28/received PY - 2017/04/11/accepted PY - 2017/5/10/pubmed PY - 2018/3/27/medline PY - 2017/5/7/entrez KW - C57BL/6J mice KW - Ethanol consumption KW - Phosphodiesterase-4 (PDE4) KW - Roflumilast KW - cAMP signaling SP - 2409 EP - 2419 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 234 IS - 16 N2 - 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. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/28477089/The_phosphodiesterase_4_inhibitor_roflumilast_decreases_ethanol_consumption_in_C57BL/6J_mice_ L2 - https://dx.doi.org/10.1007/s00213-017-4631-8 DB - PRIME DP - Unbound Medicine ER -