1. Ruey-Ming Liao Institute of NeuroscienceDepartment of PsychologyResearch Center for Mind, Brain and Learning National Cheng-Chi University Nov. 23, 2009

2. Brain Dopamine and Reward Learning 3. 54 years ago, James Olds and Peter Milner at McGill University discovered Intracranial Self Stimulation (ICSS). 4. Dopamine systems in the brain Origins: Substantia nigra (A9) Ventral tegmental area (A10) Dopamine pathways: Nigrostriatal: A9 to striatum Mesolimbic: A10 to nucleus accumbens Mesocortical: A10 to prefrontal cortexA9A10 5. a bottom-up perspective of dopamine reward - any top-down cognitive involvement ??< Phillips, Vacca & Ahn (2008) Pharmacol Biochem Behav, 90: 236-249 > 6. Why conditioned behavior? Behavior can be classified into three levels in terms of learning theory in psychobiology reflexive or non-learned: locomotor activity stimulus-response (S-R) conditioning Classical (Pavlovian) conditioning / S-S Operant (instrumental) conditioning / R-S cognition 7. Animal behavioral models (of the rat) conditioned place preference contrast choice Pharmacological treatments amphetamine & dopamine receptor blocker Neurotoxic lesions in dopamine related areas of the brain 8. Conditioned Place Preference (CPP) Procedure. pretest conditioning Drug-paired. Saline-paired. posttest 9. amphetamine or cocaine Liao et al. (1998) Chin J Physiol 41: 85-92 10. AMP or COC Liao et al. (2000) Life Sci, 67, 2033-2043 11. (SCH & RAC) AMP350 *saline-pairedamphetamine-paired 280TIME (sec) 210 140 70 8 78 8 70 Vehicle1g 10g1g10gSCH23390 Raclopride Liao (2008) Pharmacol Biochem Behav 89(3): 367-373. 12. Contrast: reward value comparison Negative contrast () 32 % down to 4 % Anticipatory contrast 4% now, but 32% later 13. Successivenegativecontrast(SNC) B1 B2 Control4% 4%groupSucrose Sucrose (unshifted) solution solutionB1 B2Contrast 32%4% group Sucrose Sucrose(shifted)solution solution LickingfrequencyshiftedTrainingsessions(days) 14. Automatedlickometer (singletubeforSNC) 15. Benzodiazepines& negative contrast Systemic injection of diazepam attenuates the negative contrast as manipulated by shifting sucrose solution from 32% down to 4 %.Liao & Chuang (2003) Pharmacol. Biochem. Behav., 74: 953-960 16. Local infusion of diazepam into amygdala, but notdorsal hippocampus, attenuated negative contrast. Liao & Chuang (2003) Pharmacol. Biochem. Behav., 74: 953-960 17. Most of previous data show that benzodiazepines encounter the anxiety reaction under the negative contrast.Q: Is brain dopamine involved in the negative contrast? 18. Decreased DAefflux in nucleusaccumbens andsuccessivenegative contrast Phillips et al (2008) Pharmacol Biochem Behav, 90: 236-249 19. increased DA efflux in nucleus accumbens and successive positive contrast Phillips et al (2008) Pharmacol Biochem Behav, 90: 236-49 20. Anticipatorycontrast(AC)B1 B2Control4% Interval(ISI)30s 4% group SucroseSucrose(unshifted)solutionsolutionB2B1 Contrast4%32% Interval(ISI)30sgroupSucrose (shifted)Sucrose solution solution Lickingfrequency,B2 Lickingfrequency,B1 Trainingsessions(days)Training sessions (days) 21. Automatedlickometer (doubletubesforAC) 22. orbitofrontal cortex; OFC nucleus accumbens core;NACc basolateral amygdala;BLA 23. Lesion of OFC attenuated AC effects OFC Sham Lesion 10B1 B2 Licking Volume (ml) 8 * * * * * * * 6 * * * * 424% - 4% (n = 7)4% - 32% (n = 7) 00 1 2 3 4 5 6 7 8 9 10 11 12 13 14 1 2 3 4 5 6 7 8 9 10 11 12 13 14Days OFC Lesion 10 B1B2 Licking Volume (ml)8 *6 4 24% - 4% ( n = 7)4% - 32% (n = 8)00 1 2 3 4 5 6 7 8 9 10 11 12 13 14 1 2 3 4 5 6 7 8 9 10 11 12 13 14Days 24. Lesion of NACc attenuated AC effectsNACc Sham Lesion 10 B1 B2 Licking Volume (ml) 8* * * * * * * * *6 4 24% - 4% (n = 8)4% - 32% (n = 8)00 1 2 3 4 5 6 7 8 9 10 11 12 13 14 1 2 3 4 5 6 7 8 9 10 11 12 13 14DaysNACc Lesion 10B1 B2 Licking Volume (ml) 86424% - 4% (n = 7)4% - 32% (n = 8) 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 1 2 3 4 5 6 7 8 9 10 11 12 13 14Days 25. Lesion of BLA did not affect AC effects BLA Sham Lesion10B1B2 Liking Volume (ml)8* * * * 6* * * *** * 42 4% - 4% (n = 7) 4% - 32% (n = 8) 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Days BLA Lesion10B1B2Licking Volume (ml) 8 * * 6* * * * * * 4*2 4% - 4% (n = 6) 4% - 32% (n = 8) 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 1 2 3 4 5 6 7 8 9 10 11 12 13 14Days 26. Is brain dopamine related to higher order cognition?behavior learned beyond S-R association 27. Run-climb-run (RCR) behavioral task a goal-directed behavior based on reward motivation dopamine dependent- SCH23390 & raclopride suppress RCR from simple motivation to complex choice Any motivated behavior can be based on the analysis of cost and benefit. 28. Choice on RCR: (high cost high benefit vs. low cost low benefit) Training phase 1: short ropeTraining phase 2: long ropeTest: concurrence choice task 29. Nucleus accumbens, but not dorsolateral striatum, involved in the choice response on a run-climb- run behavioral task 100 100808060 60 4040 20 20 0 0 30. Limbic circuitry involved in drugreward and addiction behaviorEveritt & Robbins (2005) Nat. Neurosci. 8:1481-9 31. Stimulant (cocaine) induced D1 receptor associated intracellular signaling events Anderson & Pierce (2005) Pharmacol & Therap 106:389-403 32. 33. Society for Neuroscience 1970 34. Society for Neuroscience 2009 2009 35. Journal of Neuroscience 36. Research Center for Mind, Brain, and Learning 37. 38. 39. Affective Neuroeconomics Neuroscience Computational Neuroscience Educational Neuroscience 40. 2007-2009 SCI SSCI 41. 2007-2009 SCI SSCI Impact Factor 42. 2007-2009 SCI SSCI Impact Factor, IF ) 3.5SCI3SSCISCI SSCIIF 2.5 2 1.5 1 0.52007 2008 2009 43. 2007/IF 1.4 2.3 44. - - - 45. neuropsychopharmacology - - 46. - 47. - - Board of Society for Neuroeconomics 48. - 31783- 33089- 31276*3 - 3- MRI / MEG 22.6 49. 50. a learning brain in our mind 51. acknowledgement National Science Council those students worked in my lab 52. Thank you for your attentiondriven by dopamine