Apremilast Alters Behavioral Responses to Ethanol in Mice: I. Reduced Consumption and Preference

Alcoholism, Clinical and Experimental Research
Yuri A BlednovR Adron Harris

Abstract

Phosphodiesterase type 4 (PDE4) inhibitors produce widespread anti-inflammatory effects and reduce ethanol (EtOH) consumption in several rodent models. These drugs are potential treatments for several diseases, including central nervous system disorders, but clinical use is limited by their emetic activity. Apremilast is a selective PDE4 inhibitor with fewer gastrointestinal side effects that is FDA-approved for the treatment of psoriasis. We measured the acute and chronic effects of apremilast on EtOH consumption in male and female C57BL/6J mice using the continuous and intermittent 24-hour 2-bottle choice drinking models. We also studied the effects of apremilast on preference for sucrose or saccharin, spontaneous locomotor activity, and blood EtOH clearance. Finally, apremilast levels in plasma, liver, and brain were measured 1 or 2 hours after injection. In the continuous and intermittent drinking tests, apremilast (15 to 50 mg/kg, p.o.) dose dependently reduced EtOH intake and preference in male and female mice. Higher doses of apremilast (30 to 50 mg/kg) also reduced total fluid intake in these mice. Chronic administration of apremilast (20 mg/kg) produced a stable reduction in EtOH consumption in both drinking tests with...Continue Reading

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Citations

Feb 23, 2018·Alcoholism, Clinical and Experimental Research·Yuri A BlednovRobert O Messing
Jul 19, 2018·Expert Opinion on Investigational Drugs·Leigh C Walker, Andrew J Lawrence
Dec 4, 2020·Cellular & Molecular Immunology·Hua WangYaron Rotman
Aug 4, 2021·Brain, Behavior, and Immunity·Lindsay R MeredithLara A Ray
Aug 26, 2021·Psoriasis : Targets and Therapy·Murlidhar RajagopalanPravin Banodkar

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