PMID- 24755889 OWN - NLM STAT- MEDLINE DCOM- 20150415 LR - 20211021 IS - 1740-634X (Electronic) IS - 0893-133X (Print) IS - 0893-133X (Linking) VI - 39 IP - 10 DP - 2014 Sep TI - Adenosinergic regulation of striatal clock gene expression and ethanol intake during constant light. PG - 2432-40 LID - 10.1038/npp.2014.94 [doi] AB - Circadian rhythm and sleep disruptions occur frequently in individuals with alcohol use disorders (AUD) and present significant barriers to treatment. Recently, a variant of adenosine transporter, equilibrative nucleoside transporter 1 (ENT1), was associated with the co-occurrence of sleep problems and AUD. We have previously shown that mice lacking ENT1 (ENT1 KO) have reduced adenosine levels in the striatum and drink more alcohol compared with wild types (WT). However, it is unknown whether ENT1 deletion disrupts circadian rhythms, which may contribute to alcohol preference in ENT1 KO mice. Here we used these mice to determine whether endogenous adenosine regulates circadian genetic and behavioral rhythms and influences alcohol intake during chronodisruption. We examined circadian locomotor activity in ENT1 KO vs WT littermates and found that ENT1 KO mice were both active earlier and hyperactive compared with WT mice at night. We used real-time PCR and immunohistochemistry to estimate striatal clock gene levels and found that PER2 expression in the striatum was blunted by ENT1 deletion or A2A receptor (A2AR) antagonism. Next, we exposed ENT1 KO and WT mice to constant light (LL) and found further elevation in ethanol intake in ENT1 KO, but not in WT mice, supporting the notion that circadian dysfunction may contribute to increased alcohol intake in ENT1 KO mice. Finally, we showed that A2AR agonist administration normalized PER1 and PER2 expression and circadian locomotor activity in ENT1 KO mice. Together, our results demonstrate that adenosine signaling regulates cellular and behavioral circadian timing and influences alcohol intake during chronodisruption. FAU - Ruby, Christina L AU - Ruby CL AD - 1] Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN, USA [2] Department of Biology, Indiana University of Pennsylvania, Indiana, PA, USA. FAU - Vadnie, Chelsea A AU - Vadnie CA AD - Neurobiology of Disease Program, Mayo Clinic College of Medicine, Rochester, MN, USA. FAU - Hinton, David J AU - Hinton DJ AD - Neurobiology of Disease Program, Mayo Clinic College of Medicine, Rochester, MN, USA. FAU - Abulseoud, Osama A AU - Abulseoud OA AD - Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, MN, USA. FAU - Walker, Denise L AU - Walker DL AD - Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, MN, USA. FAU - O'Connor, Katheryn M AU - O'Connor KM AD - Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN, USA. FAU - Noterman, Maria F AU - Noterman MF AD - Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN, USA. FAU - Choi, Doo-Sup AU - Choi DS AD - 1] Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN, USA [2] Neurobiology of Disease Program, Mayo Clinic College of Medicine, Rochester, MN, USA [3] Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, MN, USA. LA - eng GR - R01 AA018779/AA/NIAAA NIH HHS/United States GR - UL1 TR000135/TR/NCATS NIH HHS/United States GR - AA018779/AA/NIAAA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20140423 PL - England TA - Neuropsychopharmacology JT - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JID - 8904907 RN - 0 (Adenosine A2 Receptor Agonists) RN - 0 (Adenosine A2 Receptor Antagonists) RN - 0 (Central Nervous System Depressants) RN - 0 (Equilibrative Nucleoside Transporter 1) RN - 0 (Per1 protein, mouse) RN - 0 (Per2 protein, mouse) RN - 0 (Period Circadian Proteins) RN - 0 (Receptor, Adenosine A2A) RN - 0 (SLC29A1 protein, mouse) RN - 3K9958V90M (Ethanol) SB - IM MH - Adenosine A2 Receptor Agonists/pharmacology MH - Adenosine A2 Receptor Antagonists/pharmacology MH - Alcohol Drinking/*physiopathology MH - Animals MH - Central Nervous System Depressants/administration & dosage MH - Circadian Rhythm/drug effects/*physiology MH - Corpus Striatum/drug effects/*physiopathology MH - Equilibrative Nucleoside Transporter 1/genetics/*metabolism MH - Ethanol/administration & dosage MH - Gene Expression MH - Light MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Motor Activity/drug effects/*physiology MH - Period Circadian Proteins/metabolism MH - Photic Stimulation MH - Receptor, Adenosine A2A/*metabolism PMC - PMC4138755 EDAT- 2014/04/24 06:00 MHDA- 2015/04/16 06:00 PMCR- 2015/09/01 CRDT- 2014/04/24 06:00 PHST- 2014/01/09 00:00 [received] PHST- 2014/04/09 00:00 [revised] PHST- 2014/04/17 00:00 [accepted] PHST- 2014/04/24 06:00 [entrez] PHST- 2014/04/24 06:00 [pubmed] PHST- 2015/04/16 06:00 [medline] PHST- 2015/09/01 00:00 [pmc-release] AID - npp201494 [pii] AID - 10.1038/npp.2014.94 [doi] PST - ppublish SO - Neuropsychopharmacology. 2014 Sep;39(10):2432-40. doi: 10.1038/npp.2014.94. Epub 2014 Apr 23.