title: Imbalanced decision hierarchy in addicts emerging from drug-hijacked dopamine spiraling circuit.
abstract: Despite explicitly wanting to quit, long-term addicts find themselves powerless to resist drugs, despite knowing that drug-taking may be a harmful course of action. Such inconsistency between the explicit knowledge of negative consequences and the compulsive behavioral patterns represents a cognitive/behavioral conflict that is a central characteristic of addiction. Neurobiologically, differential cue-induced activity in distinct striatal subregions, as well as the dopamine connectivity spiraling from ventral striatal regions to the dorsal regions, play critical roles in compulsive drug seeking. However, the functional mechanism that integrates these neuropharmacological observations with the above-mentioned cognitive/behavioral conflict is unknown. Here we provide a formal computational explanation for the drug-induced cognitive inconsistency that is apparent in the addicts' "self-described mistake". We show that addictive drugs gradually produce a motivational bias toward drug-seeking at low-level habitual decision processes, despite the low abstract cognitive valuation of this behavior. This pathology emerges within the hierarchical reinforcement learning framework when chronic exposure to the drug pharmacologically produces pathologicaly persistent phasic dopamine signals. Thereby the drug hijacks the dopaminergic spirals that cascade the reinforcement signals down the ventro-dorsal cortico-striatal hierarchy. Neurobiologically, our theory accounts for rapid development of drug cue-elicited dopamine efflux in the ventral striatum and a delayed response in the dorsal striatum. Our theory also shows how this response pattern depends critically on the dopamine spiraling circuitry. Behaviorally, our framework explains gradual insensitivity of drug-seeking to drug-associated punishments, the blocking phenomenon for drug outcomes, and the persistent preference for drugs over natural rewards by addicts. The model suggests testable predictions and beyond that, sets the stage for a view of addiction as a pathology of hierarchical decision-making processes. This view is complementary to the traditional interpretation of addiction as interaction between habitual and goal-directed decision systems.
authors: Group for Neural Theory, INSERM U960, Departément des Etudes Cognitives, Ecole Normale Supérieure, Paris, France. Mr.Mehdi.Keramati@gmail.com
authors: Mehdi
authors: M
authors: Keramati
authors: Boris
authors: B
authors: Gutkin
mesh_terms: D000465:Algorithms; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D016739:Behavior, Addictive / Q000523:psychology*; D003198:Computer Simulation; D003463:Cues; D003657:Decision Making; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D008960:Models, Psychological; D009042:Motivation; D012054:Reinforcement, Psychology; D012201:Reward; D019966:Substance-Related Disorders / Q000523:psychology*
chemical_list: D004298:Dopamine
references: Front Neurosci. 2008 Jul 09;2(1):86-99
references: 18982111
references: Neural Comput. 2009 Oct;21(10):2869-93
references: 19635010
references: Eur J Neurosci. 2012 Apr;35(7):1036-51
references: 22487034
references: Proc Natl Acad Sci U S A. 1988 Jul;85(14):5274-8
references: 2899326
references: J Chem Neuroanat. 2003 Dec;26(4):317-30
references: 14729134
references: Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20703-8
references: 23184975
references: Pharmacopsychiatry. 2009 May;42 Suppl 1:S56-65
references: 19434556
references: Behav Brain Sci. 2008 Aug;31(4):415-37; discussion 437-87
references: 18662461
references: Annu Rev Neurosci. 1986;9:357-81
references: 3085570
references: Prog Brain Res. 1990;85:119-46
references: 2094891
references: Neural Comput. 2010 Sep 1;22(9):2334-68
references: 20569176
references: Behav Brain Res. 2009 Apr 12;199(1):89-102
references: 18950658
references: J Neurosci. 2005 Sep 21;25(38):8665-70
references: 16177034
references: Science. 2004 Dec 10;306(5703):1944-7
references: 15591205
references: Neuron. 2008 Feb 7;57(3):432-41
references: 18255035
references: J Mol Cell Biol. 2009 Oct;1(1):15-6
references: 19770170
references: J Pharmacol Exp Ther. 1991 Dec;259(3):1165-73
references: 1762068
references: Science. 2004 Aug 13;305(5686):1017-9
references: 15310907
references: Annu Rev Clin Psychol. 2010;6:551-75
references: 20192786
references: Nat Neurosci. 2009 Apr;12(4):515-22
references: 19252496
references: Neural Netw. 2006 Oct;19(8):1242-54
references: 16987637
references: J Neurosci. 2000 Mar 15;20(6):2369-82
references: 10704511
references: Nat Neurosci. 2005 Dec;8(12):1704-11
references: 16286932
references: Cognition. 2009 Dec;113(3):262-280
references: 18926527
references: Science. 2003 Nov 14;302(5648):1181-5
references: 14615530
references: Nat Neurosci. 2005 Nov;8(11):1481-9
references: 16251991
references: Science. 2004 Aug 13;305(5686):1014-7
references: 15310906
references: Nature. 2009 Jun 11;459(7248):837-41
references: 19448610
references: Trends Cogn Sci. 2008 May;12(5):201-8
references: 18420448
references: Pharmacol Biochem Behav. 2007 Apr;86(4):774-7
references: 17445874
references: Mol Psychiatry. 2004 Jun;9(6):557-69
references: 15098002
references: J Neurosci. 2006 Jun 14;26(24):6583-8
references: 16775146
references: J Psychopharmacol. 2010 Feb;24(2):257-66
references: 18801822
references: Science. 1997 Mar 14;275(5306):1593-9
references: 9054347
references: Am J Psychiatry. 2005 Aug;162(8):1403-13
references: 16055761
references: Nat Rev Neurosci. 2009 Sep;10(9):659-69
references: 19672274