Hernandez, Giovanni and Breton, Yannick-André and Conover, Kent and Shizgal, Peter (2010) At What Stage of Neural Processing Does Cocaine Act to Boost Pursuit of Rewards? PLoS ONE, 5 (11). e15081. ISSN 1932-6203
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Official URL: http://dx.doi.org/10.1371/journal.pone.0015081
Dopamine-containing neurons have been implicated in reward and decision making. One element of the supporting evidence is that cocaine, like other drugs that increase dopaminergic neurotransmission, powerfully potentiates reward seeking. We analyze this phenomenon from a novel perspective, introducing a new conceptual framework and new methodology for determining the stage(s) of neural processing at which drugs, lesions and physiological manipulations act to influence reward-seeking behavior. Cocaine strongly boosts the proclivity of rats to work for rewarding electrical brain stimulation. We show that the conventional conceptual framework and methods do not distinguish between three conflicting accounts of how the drug produces this effect: increased sensitivity of brain reward circuitry, increased gain, or decreased subjective reward costs. Sensitivity determines the stimulation strength required to produce a reward of a given intensity (a measure analogous to the KM of an enzyme) whereas gain determines the maximum intensity attainable (a measure analogous to the vmax of an enzyme-catalyzed reaction). To distinguish sensitivity changes from the other determinants, we measured and modeled reward seeking as a function of both stimulation strength and opportunity cost. The principal effect of cocaine was a two-fourfold increase in willingness to pay for the electrical reward, an effect consistent with increased gain or decreased subjective cost. This finding challenges the long-standing view that cocaine increases the sensitivity of brain reward circuitry. We discuss the implications of the results and the analytic approach for theories of how dopaminergic neurons and other diffuse modulatory brain systems contribute to reward pursuit, and we explore the implications of the conceptual framework for the study of natural rewards, drug reward, and mood.
|Divisions:||Concordia University > Faculty of Arts and Science > Psychology|
Concordia University > Research Units > Centre for Studies in Behavioural Neurobiology
|Authors:||Hernandez, Giovanni and Breton, Yannick-André and Conover, Kent and Shizgal, Peter|
|Journal or Publication:||PLoS ONE|
|Date:||30 November 2010|
|Digital Object Identifier (DOI):||10.1371/journal.pone.0015081|
|Keywords:||brain stimulation reward decision making dopamine psychomotor stimulants|
|Deposited By:||PETER SHIZGAL|
|Deposited On:||22 Mar 2011 21:54|
|Last Modified:||24 Aug 2016 21:26|
1. Shadlen MN, Newsome WT (1996) Motion perception: seeing and deciding. Proc Natl Acad Sci U S A 93: 628-633.
2. Shizgal P (1997) Neural basis of utility estimation. Curr Opin Neurobiol 7: 198-208.
3. Bechara A, Damasio H, Tranel D, Damasio AR (1997) Deciding advantageously before knowing the advantageous strategy. Science 275: 1293-1295.
4. McCabe K, Houser D, Ryan L, Smith V, Trouard T (2001) A functional imaging study of cooperation in two-person reciprocal exchange. Proc Natl Acad Sci U S A 98: 11832-11835.
5. Glimcher PW (2003) Decisions, uncertainty, and the brain : the science of neuroeconomics. Cambridge, Mass.: MIT Press. xx, 375 p. p.
6. Glimcher PW, Rustichini A (2004) Neuroeconomics: the consilience of brain and decision. Science 306: 447-452.
7. Tom SM, Fox CR, Trepel C, Poldrack RA (2007) The neural basis of loss aversion in decision-making under risk. Science 315: 515-518.
8. Romo R, Salinas E (2001) Touch and go: decision-making mechanisms in somatosensation. Annu Rev Neurosci 24: 107-137.
9. Trepel C, Fox CR, Poldrack RA (2005) Prospect theory on the brain? Toward a cognitive neuroscience of decision under risk. Brain Res Cogn Brain Res 23: 34-50.
10. Fellows LK (2004) The cognitive neuroscience of human decision making: a review and conceptual framework. Behav Cogn Neurosci Rev 3: 159-172.
11. Bechara A, Damasio H, Damasio AR (2000) Emotion, decision making and the orbitofrontal cortex. Cereb Cortex 10: 295-307.
12. Dolan RJ (2002) Emotion, cognition, and behavior. Science 298: 1191-1194.
13. Salzman CD, Fusi S (2010) Emotion, cognition, and mental state representation in amygdala and prefrontal cortex. Annu Rev Neurosci 33: 173-202.
14. Schultz W, Dayan P, Montague PR (1997) A neural substrate of prediction and reward. Science 275: 1593-1599.
15. Balleine BW, Delgado MR, Hikosaka O (2007) The role of the dorsal striatum in reward and decision-making. J Neurosci 27: 8161-8165.
16. Cisek P, Kalaska JF (2005) Neural correlates of reaching decisions in dorsal premotor cortex: specification of multiple direction choices and final selection of action. Neuron 45: 801-814.
17. Milstein DM, Dorris MC (2007) The influence of expected value on saccadic preparation. J Neurosci 27: 4810-4818.
18. Speakman JR (2008) The physiological costs of reproduction in small mammals. Philos Trans R Soc Lond B Biol Sci 363: 375-398.
19. Olds J, Milner PM (1954) Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain. Journal of Comparative and Physiological Psychology 47: 419-427.
20. Olds J (1958) Satiation effects in self-stimulation of the brain. J Comp Physiol Psychol 51: 675-678.
21. Montague PR, Dayan P, Sejnowski TJ (1996) A framework for mesencephalic dopamine systems based on predictive Hebbian learning. J Neurosci 16: 1936-1947.
22. Wise RA, Rompre PP (1989) Brain dopamine and reward. Annu Rev Psychol 40: 191-225.
23. Crow TJ (1970) Enhancement of coaine of intra-cranial self-stimulation in the rat. Life Sci 9: 375-381.
24. Esposito RU, Motola AH, Kornetsky C (1978) Cocaine: acute effects on reinforcement thresholds for self-stimulation behavior to the medial forebrain bundle. Pharmacol Biochem Behav 8: 437-439.
25. Salamone JD, Correa M, Mingote SM, Weber SM (2005) Beyond the reward hypothesis: alternative functions of nucleus accumbens dopamine. Curr Opin Pharmacol 5: 34-41.
26. Salamone JD, Cousins MS, Snyder BJ (1997) Behavioral functions of nucleus accumbens dopamine: empirical and conceptual problems with the anhedonia hypothesis. Neurosci Biobehav Rev 21: 341-359.
27. Hernandez G, Hamdani S, Rajabi H, Conover K, Stewart J, et al. (2006) Prolonged rewarding stimulation of the rat medial forebrain bundle: neurochemical and behavioral consequences. Behavioral Neuroscience 120: 888-904.
28. Arvanitogiannis A, Shizgal P (2008) The reinforcement mountain: allocation of behavior as a function of the rate and intensity of rewarding brain stimulation. Behav Neurosci 122: 1126-1138.
29. Olds J (1958) Self-stimulation of the brain; its use to study local effects of hunger, sex, and drugs. Science 127: 315-324.
30. Olds J, Killam KF, Bach-Y-Rita P (1956) Self-stimulation of the brain used as a screening method for tranquilizing drugs. Science 124: 265-266.
31. Liebman JM, Butcher LL (1974) Comparative involvement of dopamine and noradrenaline in rate-free self-stimulation in substania nigra, lateral hypothalamus, and mesencephalic central gray. Naunyn Schmiedebergs Arch Pharmacol 284: 167-194.
32. Valenstein ES, Meyers WJ (1964) Rate-Independent Test of Reinforcing Consequences of Brain Stimulation. J Comp Physiol Psychol 57: 52-60.
33. Fouriezos G, Bielajew C, Pagotto W (1990) Task difficulty increases thresholds of rewarding brain stimulation. Behavioural Brain Research 37: 1-7.
34. Frank RA, Williams HP (1985) Both response effort and current intensity affect self-stimulation train duration thresholds. Pharmacology Biochemistry and Behavior 22: 527-530.
35. Edmonds DE, Gallistel CR (1974) Parametric analysis of brain stimulation reward in the rat: III. Effect of performance variables on the reward summation function. Journal of Comparative and Physiological Psychology 87: 876-883.
36. Edmonds DE, Gallistel CR (1977) Reward versus performance in self-stimulation: electrode-specific effects of alpha-methyl-p-tyrosine on reward in the rat. J Comp Physiol Psychol 91: 962-974.
37. Miliaressis E, Rompre PP, Laviolette P, Philippe L, Coulombe D (1986) The curve-shift paradigm in self-stimulation. Physiology and Behavior 37: 85-91.
38. Breton YA, Marcus JC, Shizgal P (2009) Rattus Psychologicus: construction of preferences by self-stimulating rats. Behav Brain Res 202: 77-91.
39. Gallistel CR (1978) Self-stimulation in the rat: Quantitative characteristics of the reward pathway. Journal of Comparative and Physiological Psychology 92: 977-998.
40. Gallistel CR, Shizgal P, Yeomans JS (1981) A portrait of the substrate for self-stimulation. Psychological Review 88: 228-273.
41. Simmons JM, Gallistel CR (1994) Saturation of subjective reward magnitude as a function of current and pulse frequency. Behavioral Neuroscience 108: 151-160.
42. Sonnenschein B, Conover K, Shizgal P (2003) Growth of brain stimulation reward as a function of duration and stimulation strength. Behav Neurosci 117: 978-994.
43. Gallistel CR, Stellar JR, Bubis E (1974) Parametric analysis of brain stimulation reward in the rat: I. The transient process and the memory-containing process. J Comp Physiol Psychol 87: 848-859.
44. Baum WM, Rachlin HC (1969) Choice as time allocation. Journal of the Experimental Analysis of Behavior 12: 861-874.
45. Killeen P (1972) The matching law. J Exp Anal Behav 17: 489-495.
46. Miller HL (1976) Matching-based hedonic scaling in the pigeon. Journal of the Experimental Analysis of Behavior 26: 335-347.
47. Herrnstein RJ (1970) On the law of effect. Journal of the Experimental Analysis of Behavior 13: 243-266.
48. Herrnstein RJ (1974) Formal properties of the matching law. Journal of the Experimental Analysis of Behavior 21: 159-164.
49. Heyman G (1988) How drugs affect cells and reinforcement affects behavior: Formal analogies. In: Commons ML, Church RM, editors. Biological determinants of reinforcement Quantitative analyses of behavior, Vol 7. Hillsdale, NJ, England: Lawrence Erlbaum Associates, Inc. pp. 157-182.
50. Esposito R, Kornetsky C (1977) Morphine lowering of self-stimulation thresholds: Lack of tolerance with long-term administration. Science v: 189-191.
51. Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates. Amsterdam ; Boston ;: Academic Press/Elsevier. 1 v. (unpaged) p.
52. Efron B, Tibshirani R (1993) An introduction to the bootstrap. New York: Chapman & Hall. xvi, 436 p. p.
53. Akaike H (1974) A new look at the statistical model identification. IEEE transactions on automatic control 19: 716-723.
54. Aragona BJ, Cleaveland NA, Stuber GD, Day JJ, Carelli RM, et al. (2008) Preferential enhancement of dopamine transmission within the nucleus accumbens shell by cocaine is attributable to a direct increase in phasic dopamine release events. J Neurosci 28: 8821-8831.
55. Steffensen SC, Taylor SR, Horton ML, Barber EN, Lyle LT, et al. (2008) Cocaine disinhibits dopamine neurons in the ventral tegmental area via use-dependent blockade of GABA neuron voltage-sensitive sodium channels. Eur J Neurosci 28: 2028-2040.
56. Wise RA (1996) Addictive drugs and brain stimulation reward. Annu Rev Neurosci 19: 319-340.
57. Iversen L (2000) Neurotransmitter transporters: fruitful targets for CNS drug discovery. Mol Psychiatry 5: 357-362.
58. Hayes DJ, Graham DA, Greenshaw AJ (2009) Effects of systemic 5-HT(1B) receptor compounds on ventral tegmental area intracranial self-stimulation thresholds in rats. Eur J Pharmacol 604: 74-78.
59. Hayes DJ, Mosher TM, Greenshaw AJ (2009) Differential effects of 5-HT2C receptor activation by WAY 161503 on nicotine-induced place conditioning and locomotor activity in rats. Behav Brain Res 197: 323-330.
60. Ishida Y, Nakamura M, Ebihara K, Hoshino K, Hashiguchi H, et al. (2001) Immunohistochemical characterisation of Fos-positive cells in brainstem monoaminergic nuclei following intracranial self-stimulation of the medial forebrain bundle in the rat. Eur J Neurosci 13: 1600-1608.
61. Lin Y, de Vaca SC, Carr KD, Stone EA (2007) Role of alpha(1)-adrenoceptors of the locus coeruleus in self-stimulation of the medial forebrain bundle. Neuropsychopharmacology 32: 835-841.
62. Nicoll RA, Malenka RC, Kauer JA (1990) Functional comparison of neurotransmitter receptor subtypes in mammalian central nervous system. Physiol Rev 70: 513-565.
63. Oades RD, Halliday GM (1987) Ventral tegmental (A10) system: neurobiology. 1. Anatomy and connectivity. Brain Res 434: 117-165.
64. Grenhoff J, Nisell M, Ferre S, Aston-Jones G, Svensson TH (1993) Noradrenergic modulation of midbrain dopamine cell firing elicited by stimulation of the locus coeruleus in the rat. J Neural Transm Gen Sect 93: 11-25.
65. Bauco P, Wise RA (1997) Synergistic effects of cocaine with lateral hypothalamic brain stimulation reward: lack of tolerance or sensitization. J Pharmacol Exp Ther 283: 1160-1167.
66. Frank RA, Martz S, Pommering T (1988) The effect of chronic cocaine on self-stimulation train-duration thresholds. Pharmacology Biochemistry & Behavior 29: 755-758.
67. Kokkinidis L, McCarter BD (1990) Postcocaine depression and sensitization of brain-stimulation reward: analysis of reinforcement and performance effects. Pharmacol Biochem Behav 36: 463-471.
68. Markou A, Koob GF (1992) Construct validity of a self-stimulation threshold paradigm: effects of reward and performance manipulations. Physiol Behav 51: 111-119.
69. Leon M, Gallistel CR (1992) The function relating the subjective magnitude of brain stimulation reward to stimulation strength varies with site of stimulation. Behavioural Brain Research 52: 183-193.
70. Sutton MA, Beninger RJ (1999) Psychopharmacology of conditioned reward: evidence for a rewarding signal at D1-like dopamine receptors. Psychopharmacology (Berl) 144: 95-110.
71. Wise RA (1980) Action of drugs of abuse on brain reward systems. Pharmacol Biochem Behav 13: 213-223.
72. Niv Y, Daw ND, Joel D, Dayan P (2007) Tonic dopamine: opportunity costs and the control of response vigor. Psychopharmacology (Berl) 191: 507-520.
73. Salamone JD, Correa M, Farrar AM, Nunes EJ, Pardo M (2009) Dopamine, behavioral economics, and effort. Front Behav Neurosci 3: 13.
74. Hodos W (1961) Progressive ratio as a measure of reward strength. Science 134: 943-944.
75. Keesey RE, Goldstein MD (1968) Use of progressive fixed-ratio procedures in the assessment of intracranial reinforcement. J Exp Anal Behav 11: 293-301.
76. Petry NM, Heyman GM (1997) Rat toys, reinforcers, and response strength: An examination of the Re parameter in Herrnstein's equation. Behavioural Processes 39: 39-52.
77. Solomon RB, Conover K, Shizgal P (2007) Estimation of subjective opportunity cost in rats working for rewarding brain stimulation: further progress. Society for Neuroscience. San Diego.
78. Fulton S, Woodside B, Shizgal P (2006) Potentiation of brain stimulation reward by weight loss: Evidence for functional heterogeneity in brain reward circuitry. Behav Brain Res.
79. Moisan J, Rompre PP (1998) Electrophysiological evidence that a subset of midbrain dopamine neurons integrate the reward signal induced by electrical stimulation of the posterior mesencephalon. Brain Res 786: 143-152.
80. Chuhma N, Rayport S (2005) Synaptic actions of mesoaccumbens dopamine neurons. Cellscience reviews 2.
81. Anderson RM, Fatigati MD, Rompre PP (1996) Estimates of the axonal refractory period of midbrain dopamine neurons: their relevance to brain stimulation reward. Brain Res 718: 83-88.
82. Fiorillo C (2010) The neural basis of temporal prediction and the role of dopamine. In: Nobre K, Coull J, editors. Attention and time: Oxford University Press. pp. 273-288.
83. Yeomans JS, Maidment NT, Bunney BS (1988) Excitability properties of medial forebrain bundle axons of A9 and A10 dopamine cells. Brain Res 450: 86-93.
84. Shizgal P, Murray B (1989) Neuronal basis of intracranial self-stimulation. In: Liebman JM, Cooper SJ, editors. The neuropharmacological basis of reward. Oxford: Oxford University Press. pp. 106-163.
85. Cheer JF, Aragona BJ, Heien ML, Seipel AT, Carelli RM, et al. (2007) Coordinated accumbal dopamine release and neural activity drive goal-directed behavior. Neuron 54: 237-244.
86. Cheer JF, Heien MLAV, Garris PA, Carelli RM, Wightman RM (2005) Simultaneous dopamine and single-unit recordings reveal accumbens GABAergic responses: Implications for intracranial self-stimulation. Proceedings of the National Academy of Sciences of the United States of America 102: 19150-19155.
87. Tsai HC, Zhang F, Adamantidis A, Stuber GD, Bonci A, et al. (2009) Phasic firing in dopaminergic neurons is sufficient for behavioral conditioning. Science 324: 1080-1084.
88. Kim K, Baratta M, Yang A, Lee D, Boyden E, et al. (2010) Optical activation of dopamine neurons for 200 milliseconds is sufficient for operant reinforcement. Society for Neuroscience. San Diego, CA.
89. Bjorklund A, Dunnett SB (2007) Dopamine neuron systems in the brain: an update. Trends Neurosci 30: 194-202.
90. Schultz W (2000) Multiple reward signals in the brain. Nat Rev Neurosci 1: 199-207.
91. Schultz W (2002) Getting Formal with Dopamine and Reward. Neuron 36: 241-263.
92. Conover KL, Shizgal P (1994) Competition and summation between rewarding effects of sucrose and lateral hypothalamic stimulation in the rat. Behav Neurosci 108: 537-548.
93. Green L, Rachlin H (1991) Economic substitutablity of electrical brain stimulation, food, and water. Journal of the Experimental Analysis of Behavior 55: 133-143.
94. Shizgal P, Conover K (1996) On the neural computation of utility. Current Directions in Psychological Science 5: 37-43.
95. American Psychiatric Association., American Psychiatric Association. Task Force on DSM-IV. (2000) Diagnostic and statistical manual of mental disorders : DSM-IV-TR. Washington, DC: American Psychiatric Association. xxxvii, 943 p. p.
96. Shizgal P, Fulton S, Woodside B (2001) Brain reward circuitry and the regulation of energy balance. Int J Obes Relat Metab Disord 25 Suppl 5: S17-21.
97. Cardin JA, Carlén M, Meletis K, Knoblich U, Zhang F, et al. (2010) Targeted optogenetic stimulation and recording of neurons in vivo using cell-type-specific expression of Channelrhodopsin-2. Nature Protocols 5: 247-254.
98. Deisseroth K, Feng G, Majewska AK, Miesenböck G, Ting A, et al. (2006) Next-generation optical technologies for illuminating genetically targeted brain circuits. J Neurosci 26: 10380-10386.
99. Zhang F, Gradinaru V, Adamantidis AR, Durand R, Airan RD, et al. (2010) Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures. Nat Protoc 5: 439-456.
100. Hernandez G, Haines E, Shizgal P (2008) Potentiation of intracranial self-stimulation during prolonged subcutaneous infusion of cocaine. J Neurosci Methods 175: 79-87.
101. Hernandez GA, Conover K, Shizgal P (2009) At what stage of processing does dopamine influence performance for
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