title: Instant transformation of learned repulsion into motivational "wanting".
abstract: BACKGROUND
  Learned cues for pleasant reward often elicit desire, which, in addicts, may become compulsive. According to the dominant view in addiction neuroscience and reinforcement modeling, such desires are the simple products of learning, coming from a past association with reward outcome.
  
  
  RESULTS
  We demonstrate that cravings are more than merely the products of accumulated pleasure memories-even a repulsive learned cue for unpleasantness can become suddenly desired via the activation of mesocorticolimbic circuitry. Rats learned repulsion toward a Pavlovian cue (a briefly-inserted metal lever) that always predicted an unpleasant Dead Sea saltiness sensation. Yet, upon first reencounter in a novel sodium-depletion state to promote mesocorticolimbic reactivity (reflected by elevated Fos activation in ventral tegmentum, nucleus accumbens, ventral pallidum, and the orbitofrontal prefrontal cortex), the learned cue was instantly transformed into an attractive and powerful motivational magnet. Rats jumped and gnawed on the suddenly attractive Pavlovian lever cue, despite never having tasted intense saltiness as anything other than disgusting.
  
  
  CONCLUSIONS
  Instant desire transformation of a learned cue contradicts views that Pavlovian desires are essentially based on previously learned values (e.g., prediction error or temporal difference models). Instead desire is recomputed at reencounter by integrating Pavlovian information with the current brain/physiological state. This powerful brain transformation reverses strong learned revulsion into avid attraction. When applied to addiction, related mesocorticolimbic transformations (e.g., drugs or neural sensitization) of cues for already-pleasant drug experiences could create even more intense cravings. This cue/state transformation helps define what it means to say that addiction hijacks brain limbic circuits of natural reward.
authors: Biopsychology Department, 530 Church Street, East Hall, University of Michigan, Ann Arbor, MI 48109, USA. mikejfr@umich.edu
authors: Mike J F
authors: MJ
authors: Robinson
authors: Kent C
authors: KC
authors: Berridge
mesh_terms: D000818:Animals; D016739:Behavior, Addictive; D001921:Brain / Q000502:physiology; D003214:Conditioning, Classical / Q000502:physiology*; D003463:Cues; D005260:Female; D005508:Food Deprivation; D007858:Learning; D009042:Motivation; D057181:Pleasure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012201:Reward; D012965:Sodium Chloride; D019966:Substance-Related Disorders
chemical_list: D012965:Sodium Chloride
references: J Comp Physiol Psychol. 1970 Oct;73(1):117-22
references: 5507082
references: Science. 2004 Dec 10;306(5703):1944-7
references: 15591205
references: Behav Neurosci. 1983 Oct;97(5):746-58
references: 6639747
references: Eur J Neurosci. 2012 Apr;35(7):1124-43
references: 22487042
references: Biol Psychiatry. 2013 May 1;73(9):819-26
references: 23044182
references: J Neurosci. 2009 Sep 30;29(39):12220-8
references: 19793980
references: Nat Neurosci. 2005 Dec;8(12):1704-11
references: 16286932
references: Ann N Y Acad Sci. 1999 Jun 29;877:645-54
references: 10415676
references: PLoS Comput Biol. 2009 Jul;5(7):e1000437
references: 19609350
references: Exp Physiol. 2008 Feb;93(2):177-209
references: 17981930
references: Learn Mem. 2005 Nov-Dec;12(6):549-52
references: 16287723
references: J Comp Physiol Psychol. 1968 Apr;65(2):197-201
references: 5668303
references: Proc Natl Acad Sci U S A. 2011 Jul 26;108(30):12509-14
references: 21746918
references: Q J Exp Psychol B. 1986 May;38(2):161-72
references: 3737979
references: Neuropsychopharmacology. 2007 Nov;32(11):2267-78
references: 17406653
references: Neuropharmacology. 2009;56 Suppl 1:160-8
references: 18657553
references: Neuroendocrinology. 2003 Jun;77(6):406-15
references: 12845226
references: J Neurophysiol. 2006 Nov;96(5):2399-409
references: 16885520
references: Curr Opin Neurobiol. 2013 Apr;23(2):229-38
references: 23267662
references: Cognition. 1990 Nov;37(1-2):105-31
references: 2269004
references: Q J Exp Psychol B. 1989 May;41(2):121-38
references: 2748936
references: J Neurosci. 2009 May 20;29(20):6500-13
references: 19458221
references: J Neurosci. 2008 Jul 9;28(28):7184-92
references: 18614688
references: Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15235-9
references: 20696892
references: J Exp Psychol Anim Behav Process. 1978 Jul;4(3):276-85
references: 567670
references: J Neurosci. 2005 Dec 14;25(50):11777-86
references: 16354936
references: Appetite. 2007 Sep;49(2):353-67
references: 17561308
references: J Exp Psychol Anim Behav Process. 1986 Apr;12(2):143-52
references: 3701263
references: Neuroendocrinology. 2007;85(3):139-47
references: 17483578
references: J Neurosci. 2006 Jun 14;26(24):6583-8
references: 16775146
references: Proc Natl Acad Sci U S A. 2011 Jul 5;108(27):E255-64
references: 21670308
references: Brain Res Brain Res Rev. 1993 Sep-Dec;18(3):247-91
references: 8401595
references: Science. 1997 Mar 14;275(5306):1593-9
references: 9054347