Apremilast Alters Behavioral Responses to Ethanol in Mice: II. Increased Sedation, Intoxication, and Reduced Acute Functional Tolerance. (24th March 2018)

• Record Type: Journal Article
• Authors: Blednov, Yuri A.; Da Costa, Adriana J.; Harris, R. Adron; Messing, Robert O.
• Is Part Of: Alcoholism. Volume 42:Number 5(2018)
• Page Start: 939
• Page End: 951
• Publication Date: 2018-03-24
• Subjects: PDE4 Inhibitor -- Loss of Righting Reflex -- Acute Ethanol Withdrawal -- Acute Functional Tolerance -- C57BL/6J mice; Alcoholism -- Periodicals; Alcoholism -- Periodicals; Alcoolisme; Electronic journals; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.861005
• DOI: 10.1111/acer.13615
• Languages: English
• ISSNs: 0145-6008

Abstract

Abstract : Background: In our companion paper, we reported that the phosphodiesterase type 4 inhibitor apremilast reduced ethanol (EtOH) intake and preference in different drinking models in male and female C57BL/6J mice. In this study, we measured the effects of apremilast on other behaviors that are correlated with EtOH consumption. Methods: The effects of apremilast (20 mg/kg) on the following behaviors were studied in male and female C57BL/6J mice: locomotor response to a novel situation; EtOH‐ and lithium chloride (LiCl)‐induced conditioned taste aversion (CTA) to saccharin; conditioned place preference (CPP) and conditioned place avoidance (CPA) to EtOH; severity of handling‐induced convulsions after EtOH administration; EtOH‐induced anxiolytic‐like behavior in the elevated plus maze; duration of EtOH‐induced loss of righting reflex (LORR); recovery from EtOH‐induced motor impairment on the rotarod; and acute functional tolerance (AFT) to EtOH's ataxic effects. Results: Apremilast did not change the acquisition of EtOH‐induced CPP, severity of acute withdrawal from EtOH, or EtOH's anxiolytic‐like effect. Apremilast did not alter the extinction of EtOH‐ or LiCl‐induced CTA, but may interfere with acquisition of CTA to EtOH. Apremilast increased the acquisition of CPA to EtOH, reduced locomotor responses to a novel situation, and prolonged the duration of LORR and the recovery from acute motor incoordination induced by EtOH. The longer recovery from the ataxic effect may be attributed to reduced development of AFT to EtOH. Conclusions: Our results suggest that apremilast increases the duration of EtOH intoxication by reducing AFT. Apremilast also reduces some aspects of general reward and increases EtOH's aversive properties, which might also contribute to its ability to reduce EtOH drinking. Abstract : Our companion study showed that apremilast reduced voluntary ethanol (EtOH) consumption in different drinking models in mice. We next measured the effects of apremilast on other behaviors that are correlated with EtOH consumption. Apremilast (20 mg/kg) increased the acute hypnotic (A) and motor impairing (B) effects of EtOH and reduced acute functional tolerance (C) to the ataxic effects in male and female mice. An increase in EtOH's aversive properties could contribute to the ability of apremilast to decrease drinking.