title: Adenosine signaling in striatal circuits and alcohol use disorders.
abstract: Adenosine signaling has been implicated in the pathophysiology of alcohol use disorders and other psychiatric disorders such as anxiety and depression. Numerous studies have indicated a role for A1 receptors (A1R) in acute ethanol-induced motor incoordination, while A2A receptors (A2AR) mainly regulate the rewarding effect of ethanol in mice. Recent findings have demonstrated that dampened A2AR-mediated signaling in the dorsomedial striatum (DMS) promotes ethanol-seeking behaviors. Moreover, decreased A2AR function is associated with decreased CREB activity in the DMS, which enhances goal-oriented behaviors and contributes to excessive ethanol drinking in mice. Interestingly, caffeine, the most commonly used psychoactive substance, is known to inhibit both the A1R and A2AR. This dampened adenosine receptor function may mask some of the acute intoxicating effects of ethanol. Furthermore, based on the fact that A2AR activity plays a role in goal-directed behavior, caffeine may also promote ethanol-seeking behavior. The A2AR is enriched in the striatum and exclusively expressed in striatopallidal neurons, which may be responsible for the regulation of inhibitory behavioral control over drug rewarding processes through the indirect pathway of the basal ganglia circuit. Furthermore, the antagonistic interactions between adenosine and dopamine receptors in the striatum also play an integral role in alcoholism and addiction-related disorders. This review focuses on regulation of adenosine signaling in striatal circuits and the possible implication of caffeine in goal-directed behaviors and addiction.
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, Minnesota, 55905, USA.
authors.forename: Hyung Wook
authors.initials: HW
authors.lastname: Nam
authors.forename: Robert C
authors.initials: RC
authors.lastname: Bruner
authors.forename: Doo-Sup
authors.initials: DS
authors.lastname: Choi
mesh_terms: D000241:Adenosine / Q000378:metabolism* / Q000494:pharmacology; D000428:Alcohol Drinking; D019973:Alcohol-Related Disorders / Q000378:metabolism*; D000818:Animals; D002110:Caffeine / Q000378:metabolism / Q000494:pharmacology; D002755:Choice Behavior; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D018492:Dopamine Antagonists / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D051379:Mice; D043682:Receptor, Adenosine A1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D018492:Dopamine Antagonists; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D011954:Receptors, Dopamine; D018047:Receptors, Purinergic P1; D002110:Caffeine; D000431:Ethanol; D000241:Adenosine
references.citation: Proc Natl Acad Sci U S A. 2006 May 16;103(20):7877-82
references.pmid: 16684876
references.citation: J Neurosci Res. 2008 Sep;86(12):2641-9
references.pmid: 18478552
references.citation: J Neurosci. 1996 Oct 15;16(20):6579-91
references.pmid: 8815934
references.citation: Alcohol Clin Exp Res. 2011 Apr;35(4):584-94
references.pmid: 21223299
references.citation: Nat Neurosci. 2004 Aug;7(8):855-61
references.pmid: 15258586
references.citation: Trends Neurosci. 1997 Oct;20(10):482-7
references.pmid: 9347617
references.citation: Psychopharmacology (Berl). 1991;103(4):467-72
references.pmid: 1648247
references.citation: Nat Neurosci. 2005 Jul;8(7):858-9
references.pmid: 15965471
references.citation: Physiol Behav. 2007 Sep 10;92(1-2):210-7
references.pmid: 17572452
references.citation: Nat Neurosci. 2006 Mar;9(3):443-52
references.pmid: 16491081
references.citation: Alcohol Alcohol Suppl. 1993;2:437-41
references.pmid: 7748335
references.citation: Alcohol Clin Exp Res. 2012 Jul;36(7):1117-25
references.pmid: 22309182
references.citation: Alcohol. 1999 Oct;19(2):157-62
references.pmid: 10548160
references.citation: Eur J Neurosci. 2004 Jan;19(1):181-9
references.pmid: 14750976
references.citation: Front Behav Neurosci. 2011 Jul 28;5:47
references.pmid: 21847377
references.citation: Alcohol Clin Exp Res. 2012 Jan;36(1):4-13
references.pmid: 21762181
references.citation: Curr Drug Abuse Rev. 2010 Sep;3(3):163-74
references.pmid: 21054262
references.citation: Trends Neurosci. 2004 Aug;27(8):468-74
references.pmid: 15271494
references.citation: Pflugers Arch. 2004 Feb;447(5):735-43
references.pmid: 12838422
references.citation: J Biol Chem. 1997 Nov 7;272(45):28423-30
references.pmid: 9353301
references.citation: Prog Neurobiol. 1999 Nov;59(4):355-96
references.pmid: 10501634
references.citation: Nature. 1997 Aug 14;388(6643):674-8
references.pmid: 9262401
references.citation: Nat Neurosci. 2009 Mar;12(3):333-41
references.pmid: 19198605
references.citation: Neuropharmacology. 1997 Sep;36(9):1201-10
references.pmid: 9364475
references.citation: Eur J Pharmacol. 1996 Sep 5;311(1):45-52
references.pmid: 8884235
references.citation: Br J Pharmacol. 2000 Apr;129(7):1465-73
references.pmid: 10742303
references.citation: Neuropharmacology. 2001 Apr;40(5):722-31
references.pmid: 11311901
references.citation: J Neurosci Res. 2006 Sep;84(4):801-8
references.pmid: 16862552
references.citation: Mol Med Today. 1999 May;5(5):216-24
references.pmid: 10322314
references.citation: Prog Neurobiol. 2010 Apr;90(4):385-417
references.pmid: 19941931
references.citation: J Neurosci. 1999 Nov 1;19(21):9192-200
references.pmid: 10531422
references.citation: Trends Neurosci. 2007 May;30(5):228-35
references.pmid: 17408758
references.citation: J Neurosci. 2006 Feb 15;26(7):2080-7
references.pmid: 16481441
references.citation: Front Neuroanat. 2011 Jul 15;5:40
references.pmid: 21811438
references.citation: Neuropsychopharmacology. 2010 Jan;35(1):217-38
references.pmid: 19710631
references.citation: Glia. 2010 Aug 15;58(11):1335-44
references.pmid: 20607719
references.citation: Neuropharmacology. 2001 Mar;40(3):424-32
references.pmid: 11166335
references.citation: Alcohol Clin Exp Res. 1998 Apr;22(2):382-90
references.pmid: 9581644
references.citation: Eur Heart J. 1993 Nov;14 Suppl I:27-33
references.pmid: 8293779
references.citation: Alcohol Clin Exp Res. 2004 Sep;28(9):1308-16
references.pmid: 15365300
references.citation: Biochem J. 1994 Nov 15;304 ( Pt 1):205-10
references.pmid: 7998934
references.citation: PLoS One. 2011 Jan 24;6(1):e16331
references.pmid: 21283641
references.citation: Behav Brain Res. 2010 Apr 2;208(2):636-42
references.pmid: 20085785
references.citation: J Neurosci. 2002 Dec 1;22(23):10487-93
references.pmid: 12451148
references.citation: Trends Pharmacol Sci. 2006 Aug;27(8):416-25
references.pmid: 16820221
references.citation: Annu Rev Pharmacol Toxicol. 2005;45:385-412
references.pmid: 15822182
references.citation: J Comp Neurol. 1995 May 8;355(3):418-26
references.pmid: 7636023
references.citation: Neurosci Biobehav Rev. 2013 Nov;37(9 Pt A):1946-54
references.pmid: 23438892
references.citation: Psychopharmacology (Berl). 1997 Jan;129(2):99-111
references.pmid: 9040115
references.citation: Annu Rev Neurosci. 2008;31:359-87
references.pmid: 18558860
references.citation: Eur J Neurosci. 2007 Jun;25(11):3226-32
references.pmid: 17552991
references.citation: Neuropharmacology. 2010 Jun;58(7):951-61
references.pmid: 20096294
references.citation: J Biol Chem. 2005 Apr 22;280(16):15880-7
references.pmid: 15701636
references.citation: Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1970-5
references.pmid: 11172060
references.citation: Nat Neurosci. 2007 Nov;10(11):1395-7
references.pmid: 17934457
references.citation: Biol Psychiatry. 2011 Jun 1;69(11):1043-51
references.pmid: 21489406
references.citation: Nat Rev Neurosci. 2006 Jun;7(6):464-76
references.pmid: 16715055
references.citation: J Neurosci. 2013 Mar 6;33(10):4329-38
references.pmid: 23467349
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 1990 Oct;342(4):447-53
references.pmid: 2255336
references.citation: Brain Res. 1998 May 25;794(1):35-47
references.pmid: 9630499
references.citation: J Neurosci. 2009 Dec 2;29(48):15100-3
references.pmid: 19955361
references.citation: Alcohol Clin Exp Res. 1995 Aug;19(4):892-901
references.pmid: 7485836
references.citation: Nature. 2003 Oct 30;425(6961):917-25
references.pmid: 14586460
references.citation: Int Rev Neurobiol. 2005;63:191-270
references.pmid: 15797469
references.citation: Mol Pharmacol. 2000 Oct;58(4):771-7
references.pmid: 10999947
references.citation: Neuron. 2002 Aug 15;35(4):605-23
references.pmid: 12194863
references.citation: Cell Mol Life Sci. 2006 Nov;63(21):2427-31
references.pmid: 17058035
references.citation: CNS Neurosci Ther. 2010 Jun;16(3):e18-42
references.pmid: 20345970
references.citation: J Neurosci. 2000 Aug 15;20(16):5949-57
references.pmid: 10934242
references.citation: Annu Rev Neurosci. 2001;24:31-55
references.pmid: 11283304
references.citation: Curr Biol. 2000 Jul 13;10(14):R509-11
references.pmid: 10899013
references.citation: Ann N Y Acad Sci. 1991;625:473-87
references.pmid: 2058901
references.citation: Structure. 2011 Sep 7;19(9):1283-93
references.pmid: 21885291
references.citation: Biol Psychiatry. 2012 Sep 1;72(5):389-95
references.pmid: 22440617
references.citation: J Neurosci. 2007 Aug 1;27(31):8161-5
references.pmid: 17670959
references.citation: Psychopharmacology (Berl). 2006 Nov;189(1):117-24
references.pmid: 17047937