, Volume 203, Issue 3, pp 489–499 | Cite as

The adenosine A2A antagonist MSX-3 reverses the effort-related effects of dopamine blockade: differential interaction with D1 and D2 family antagonists

  • Lila T. Worden
  • Mona Shahriari
  • Andrew M. Farrar
  • Kelly S. Sink
  • Jörg Hockemeyer
  • Christa E. Müller
  • John D. Salamone
Original Investigation



Brain dopamine (DA) participates in the modulation of instrumental behavior, including aspects of behavioral activation and effort-related choice behavior. Rats with impaired DA transmission reallocate their behavior away from food-seeking behaviors that have high response requirements, and instead select less effortful alternatives. Although accumbens DA is considered a critical component of the brain circuitry regulating effort-related choice behavior, emerging evidence demonstrates a role for adenosine A2A receptors.


Adenosine A2A receptor antagonism has been shown to reverse the effects of DA antagonism. The present experiments were conducted to determine if this effect was dependent upon the subtype of DA receptor that was antagonized to produce the changes in effort-related choice.

Materials and methods

The adenosine A2A receptor antagonist MSX-3 (0.5–2.0 mg/kg IP) was assessed for its ability to reverse the effects of the D1 family antagonist SCH39166 (ecopipam; 0.2 mg/kg IP) and the D2 family antagonist eticlopride (0.08 mg/kg IP), using a concurrent lever pressing/chow feeding procedure.


MSX-3 produced a substantial dose-related reversal of the effects of eticlopride on lever pressing and chow intake. At the highest dose of MSX-3, there was a complete reversal of the effects of eticlopride on lever pressing. In contrast, MSX-3 produced only a minimal attenuation of the effects of SCH39166, as measured by regression and effect size analyses.


The greater ability of MSX-3 to reverse the effects of D2 vs. D1 blockade may be related to the colocalization of D2 and adenosine A2A receptors on the same population of striatal neurons.


Operant Reinforcement Motivation Behavioral economics Reward Decision making Activation 



This work was supported by a grant to J.S. from the National Institute of Mental Health (MH078023).


  1. Aberman JE, Salamone JD (1999) Nucleus accumbens dopamine depletions make rats more sensitive to high ratio requirements but do not impair primary food reinforcement. Neuroscience 92:545–552. doi: 10.1016/S0306-4522(99)00004-4 CrossRefPubMedGoogle Scholar
  2. Alburges ME, Hunt ME, McQuade RD, Wamsley JK (1992) D1-receptor antagonists: comparison of [3H]SCH39166 to [3H]SCH23390. J Chem Neuroanat 5:357–366CrossRefPubMedGoogle Scholar
  3. Baldo BA, Kelley AE (2007) Discrete neurochemical coding of distinguishable motivational processes: insights from nucleus accumbens control of feeding. Psychopharmacology (Berl) 191:439–459CrossRefGoogle Scholar
  4. Barbano MF, Cador M (2007) Opioids for hedonic experience and dopamine to get ready for it. Psychopharmacology 191:497–506CrossRefPubMedGoogle Scholar
  5. Capuron L, Pagnoni G, Demetrashvili MF, Lawson DH, Fornwalt FB, Woolwine B, Berns GS, Gregory S, Nemeroff CB, Miller AH (2007) Basal ganglia hypermetabolism and symptoms of fatigue during interferon-alpha therapy. Neuropsychopharmacology 32:2384–2392. doi: 10.1038/sj.npp.1301362 CrossRefPubMedGoogle Scholar
  6. Clifton PG (1995) Effects of SCH39166 and domperidone on the meal patterning of male rats. Pharmacol Biochem Behav 52:265–270CrossRefPubMedGoogle Scholar
  7. Clifton PG, Rusk IN, Cooper SJ (1991) Effects of dopamine D1 and dopamine D2 antagonists on the free feeding and drinking patterns of rats. Behav Neurosci 105:272–281CrossRefPubMedGoogle Scholar
  8. Correa M, Carlson BB, Wisniecki A, Salamone JD (2002) Nucleus accumbens dopamine and work requirements on interval schedules. Behav Brain Res 137:179–187. doi: 10.1016/S0166-4328(02)00292-9 CrossRefPubMedGoogle Scholar
  9. Correa M, Wisniecki A, Betz A, Dobson DR, O'Neill MF, O'Neill MJ, Salamone JD (2004) The adenosine A2A antagonist KF17837 reverses the locomotor suppression and tremulous jaw movements induced by haloperidol in rats: possible relevance to parkinsonism. Behav Brain Res 148:47–54. doi: 10.1016/S0166-4328(03)00178-5 CrossRefPubMedGoogle Scholar
  10. Cousins MS, Salamone JD (1994) Nucleus accumbens dopamine depletions in rats affect relative response allocation in a novel cost/benefit procedure. Pharmacol Biochem Behav 49:85–91. doi: 10.1016/0091-3057(94)90460-X CrossRefPubMedGoogle Scholar
  11. Cousins MS, Sokolowski JD, Salamone JD (1993) Different effects of nucleus accumbens and ventrolateral striatal dopamine depletions on instrumental response selection in the rat. Pharmacol Biochem Behav 46:953–951. doi: 10.1016/0091-3057(93)90226-J CrossRefGoogle Scholar
  12. Cousins MS, Wei W, Salamone JD (1994) Pharmacological characterization of performance on a concurrent lever pressing/feeding choice procedure: effects of dopamine antagonist, cholinomimetic, sedative and stimulant drugs. Psychopharmacology 116:529–537. doi: 10.1007/BF02247489 CrossRefPubMedGoogle Scholar
  13. Cousins MS, Atherton A, Turner L, Salamone JD (1996) Nucleus accumbens dopamine depletions alter relative response allocation in a T-maze cost/benefit task. Behav Brain Res 74:189–197. doi: 10.1016/0166-4328(95)00151-4 CrossRefPubMedGoogle Scholar
  14. DeMet EM, Chicz-DeMet A (2002) Localization of adenosine A2A-receptors in rat brain with [3H]ZM-241385. Naunyn Schmiedebergs Arch Pharmacol 366:478–481. doi: 10.1007/s00210-002-0613-3 CrossRefPubMedGoogle Scholar
  15. Demyttenaere K, De Fruyt J, Stahl SM (2005) The many faces of fatigue in major depressive disorder. Int J Neuropsychopharmacol 8:93–105. doi: 10.1017/S1461145704004729 CrossRefPubMedGoogle Scholar
  16. Denk F, Walton ME, Jennings KA, Sharp T, Rushworth MF, Bannerman DM (2005) Differential involvement of serotonin and dopamine systems in cost–benefit decisions about delay or effort. Psychopharmacology 179:587–596. doi: 10.1007/s00213-004-2059-4 CrossRefPubMedGoogle Scholar
  17. Farrar AM, Pereira M, Velasco F, Hockemeyer J, Muller CE, Salamone JD (2007) Adenosine A(2A) receptor antagonism reverses the effects of dopamine receptor antagonism on instrumental output and effort-related choice in the rat: implications for studies of psychomotor slowing. Psychopharmacology 191:579–586. doi: 10.1007/s00213-006-0554-5 CrossRefPubMedGoogle Scholar
  18. Farrar AM, Font L, Pereira M, Mingote SM, Bunce JG, Chrobak JJ, Salamone JD (2008) Forebrain circuitry involved in effort-related choice: injections of the GABAA agonist muscimol into ventral pallidum alters response allocation in food-seeking behavior. Neuroscience 152:321–330CrossRefPubMedGoogle Scholar
  19. Ferré S (1997) Adenosine-dopamine interactions in the ventral striatum. Implications for the treatment of schizophrenia. Psychopharmacology 133:107–120. doi: 10.1007/s002130050380 CrossRefPubMedGoogle Scholar
  20. Ferré S, Fredholm BB, Morelli M, Popoli P, Fuxe K (1997) Adenosine–dopamine receptor–receptor interactions as an integrative mechanism in the basal ganglia. Trends Neurosci 20:482–487. doi: 10.1016/S0166-2236(97)01096-5 CrossRefPubMedGoogle Scholar
  21. Ferré S, Popoli P, Giménez-Llort L, Rimondini R, Müller CE, Strömberg I, Ögren SO, Fuxe K (2001) Adenosine/dopamine interaction: implications for the treatment of Parkinson’s disease. Parkinsonism Relat Disord 7(3):235–241. doi: 10.1016/S1353-8020(00)00063-8 CrossRefPubMedGoogle Scholar
  22. Ferré S, Ciruela F, Canals M, Marcellino D, Burgueno J, Casado V, Hillion J, Torvinen M, Fanelli F, Benedetti Pd P, Goldberg SR, Bouvier M, Fuxe K, Agnati LF, Lluis C, Franco R, Woods A (2004) Adenosine A2A–dopamine D2 receptor–receptor heteromers. Targets for neuro-psychiatric disorders. Parkinsonism Relat Disord 10:265–271. doi: 10.1016/j.parkreldis.2004.02.014 CrossRefPubMedGoogle Scholar
  23. Ferre S, Ciruela F, Borycz J, Solinas M, Quarta D, Antoniou K, Quiroz C, Justinova Z, Lluis C, Franco R, Goldberg SR (2008) Adenosine A1–A2A receptor heteromers: new targets for caffeine in the brain. Front Biosci 13:2391–2399CrossRefPubMedGoogle Scholar
  24. Fink JS, Weaver DR, Rivkees SA, Peterfreund RA, Pollack AE, Adler EM, Reppert SM (1992) Molecular cloning of the rat A2A adenosine receptor: selective co-expression with D2 dopamine receptors in rat striatum. Brain Res Mol Brain Res 14:186–195. doi: 10.1016/0169-328X(92)90173-9 CrossRefPubMedGoogle Scholar
  25. Floresco SB, Ghods-Sharifi S (2007) Amygdala–prefrontal cortical circuitry regulates effort-based decision making. Cereb Cortex 17:251–260. doi: 10.1093/cercor/bhj143 CrossRefPubMedGoogle Scholar
  26. Floresco SB, Tse MT, Ghods-Sharifi S (2008) Dopaminergic and glutamatergic regulation of effort- and delay-based decision making. Neuropsychopharmacology 33:1966–1979. doi: 10.1038/sj.npp.1301565 CrossRefPubMedGoogle Scholar
  27. Font L, Mingote S, Farrar AM, Pereira M, Worden L, Stopper C, Port RG, Salamone JD (2008) Intra-accumbens injections of the adenosine A(2A) agonist CGS 21680 affect effort-related choice behavior in rats. Psychopharmacology 199:515–526CrossRefPubMedGoogle Scholar
  28. Fowler SC, Liou JR (1998) Haloperidol, raclopride, and eticlopride induce microcatalepsy during operant performance in rats, but clozapine and SCH 23390 do not. Psychopharmacology 140:81–90CrossRefPubMedGoogle Scholar
  29. Fuxe K, Agnati LF, Jacobsen K, Hillion J, Canals M, Torvinen M, Tinner-Staines B, Staines W, Rosin D, Terasmaa A, Popoli P, Leo G, Vergoni V, Lluis C, Ciruela F, Franco R, Ferré S (2003) Receptor heteromerization in adenosine A2A receptor signaling: relevance for striatal function and Parkinson’s disease. Neurology 61:S19–S23PubMedGoogle Scholar
  30. Fuxe K, Ferré S, Genedani S, Franco R, Agnati LF (2007) Adenosine receptor–dopamine receptor interactions in the basal ganglia and their relevance for brain function. Physiol Behav 92:210–217CrossRefPubMedGoogle Scholar
  31. Hauber W, Munkel M (1997) Motor depressant effects mediated by dopamine D2 and adenosine A2A receptors in the nucleus accumbens and the caudate-putamen. Eur J Pharmacol 323:127–31. doi: 10.1016/S0014-2999(97)00040-X CrossRefPubMedGoogle Scholar
  32. Hauber W, Neuscheler P, Nagel J, Muller CE (2001) Catalepsy induced by a blockade of dopamine D1 or D2 receptors was reversed by a concomitant blockade of adenosine A2A receptors in the caudate putamen of rats. Eur J Neurosci 14:1287–1293. doi: 10.1046/j.0953-816x.2001.01759.x CrossRefPubMedGoogle Scholar
  33. Hietala J, Seppäla T, Lappalainen J, Syvälahti E (1992) Quantification of SCH 39166, a novel selective D1 dopamine receptor antagonist, in rat brain and blood. Psychopharmacology 106:455–458CrossRefPubMedGoogle Scholar
  34. Hillion J, Canals M, Torvinen M, Casado V, Scott R, Terasmaa A, Hansson A, Watson S, Olah ME, Mallol J, Canela EI, Zoli M, Agnati LF, Ibanez CF, Lluis C, Franco R, Ferré S, Fuxe K (2002) Coaggregation, cointernalization, and codesensitization of adenosine A2A receptors and dopamine D2 receptors. J Biol Chem 277:18091–18097. doi: 10.1074/jbc.M107731200 CrossRefPubMedGoogle Scholar
  35. Hockemeyer J, Burbiel JC, Muller CE (2004) Multigram-scale syntheses, stability, and photoreactions of A2A adenosine receptor antagonists with 8-styrylxanthine structure: potential drugs for Parkinson’s disease. J Org Chem 69:3308–3318CrossRefPubMedGoogle Scholar
  36. Ishiwari K, Madson LJ, Farrar AM, Mingote SM, Valenta JP, DiGianvittorio MD, Frank LE, Correa M, Hockemeyer J, Muller C, Salamone JD (2007) Injections of the selective adenosine A2A antagonist MSX-3 into the nucleus accumbens core attenuate the locomotor suppression induced by haloperidol in rats. Behav Brain Res 178:190–199. doi: 10.1016/j.bbr.2006.12.020 CrossRefPubMedGoogle Scholar
  37. Jarvis MF, Williams M (1989) Direct autoradiographic localization of adenosine A2A receptors in the rat brain using the A2A-selective agonist, [3H]CGS 21680. Eur J Pharmacol 168:243–246. doi: 10.1016/0014-2999(89)90571-2 CrossRefPubMedGoogle Scholar
  38. Jenner P (2003) Dopamine agonists, receptor selectivity and dyskinesia induction in Parkinson’s disease. Curr Opin Neurol 16(Suppl 1):S3–S7. doi: 10.1097/00019052-200312001-00002 PubMedCrossRefGoogle Scholar
  39. Jenner P (2005) Istradefylline, a novel adenosine A2A receptor antagonist, for the treatment of Parkinson's disease. Expert Opin Investig Drugs 14:729–738. doi: 10.1517/13543784.14.6.729 CrossRefPubMedGoogle Scholar
  40. Kelley AE, Baldo BA, Pratt WE, Will MJ (2005) Corticostriatal–hypothalamic circuitry and food motivation: integration of energy, action and reward. Physiol Behav 86:773–795CrossRefPubMedGoogle Scholar
  41. Keppel G (1991) Design and analysis: a researcher’s handbook. Prentice-Hall, Englewood Cliffs, New JerseyGoogle Scholar
  42. Koch M, Schmid A, Schnitzler HU (2000) Role of muscles accumbens dopamine D1 and D2 receptors in instrumental and Pavlovian paradigms of conditioned reward. Psychopharmacology 152:67–73. doi: 10.1007/s002130000505 CrossRefPubMedGoogle Scholar
  43. Majer M, Welberg LA, Capuron L, Pagnoni G, Raison CL, Miller AH (2008) IFN-alpha-induced motor slowing is associated with increased depression and fatigue in patients with chronic hepatitis C. Brain Behav Immun 22:870–880. doi: 10.1016/j.bbi.2007.12.009 CrossRefPubMedGoogle Scholar
  44. Mingote S, Weber SM, Ishiwari K, Correa M, Salamone JD (2005) Ratio and time requirements on operant schedules: effort-related effects of nucleus accumbens dopamine depletions. Eur J Neurosci 21:1749–1757CrossRefPubMedGoogle Scholar
  45. Mingote S, Font L, Farrar AM, Vontell R, Worden LT, Stopper CM, Port RG, Sink KS, Bunce JG, Chrobak JJ, Salamone JD (2008) Nucleus accumbens adenosine A2A receptors regulate exertion of effort by acting on the ventral striatopallidal pathway. J Neurosci 28:9037–9046CrossRefPubMedGoogle Scholar
  46. Morelli M, Pinna A (2002) Interaction between dopamine and adenosine A2A receptors as a basis for the treatment of Parkinson’s disease. Neurol Sci 22:71–72. doi: 10.1007/s100720170052 CrossRefGoogle Scholar
  47. Niv Y, Daw ND, Joel D, Dayan P (2007) Tonic dopamine: opportunity costs and the control of response vigor. Psychopharmacology 191:507–520. doi: 10.1007/s00213-006-0502-4 CrossRefPubMedGoogle Scholar
  48. Nowend KL, Arizzi M, Carlson BB, Salamone JD (2001) D1 or D2 antagonism in nucleus accumbens core or dorsomedial shell suppresses lever pressing for food but leads to compensatory increases in chow consumption. Pharmacol Biochem Behav 69:373–382. doi: 10.1016/S0091-3057(01)00524-X CrossRefPubMedGoogle Scholar
  49. O'Neill M, Brown VJ (2006) The effect of the adenosine A2A antagonist KW-6002 on motor and motivational processes in the rat. Psychopharmacology 184:46–55. doi: 10.1007/s00213-005-0240-z CrossRefPubMedGoogle Scholar
  50. Phillips PE, Walton ME, Jhou TC (2007) Calculating utility: preclinical evidence for cost–benefit analysis by mesolimbic dopamine. Psychopharmacology 191:483–495. doi: 10.1007/s00213-006-0626-6 CrossRefPubMedGoogle Scholar
  51. Pinna A, Wardas J, Cozzolino A, Morelli M (1999) Involvement of adenosine A2A receptors in the induction of c-fos expression by clozapine and haloperidol. Neuropsychopharmacology 20:44–51CrossRefPubMedGoogle Scholar
  52. Pinna A, Wardas J, Simola N, Morelli M (2005) New therapies for the treatment of Parkinson’s disease: adenosine A2A receptor antagonists. Life Sci 77:3259–3267. doi: 10.1016/j.lfs.2005.04.029 CrossRefPubMedGoogle Scholar
  53. Salamone JD (1991) Behavioral pharmacology of dopamine systems: a new synthesis. In: Willner P, Scheel-Kruger J (eds) The mesolimbic dopamine system: from motivation to action. Cambridge University Press, Cambridge, England, pp 599–613Google Scholar
  54. Salamone JD (1992) Complex motor and sensorimotor functions of striatal and accumbens dopamine: involvement in instrumental behavior processes. Psychopharmacology 107:160–174. doi: 10.1007/BF02245133 CrossRefPubMedGoogle Scholar
  55. Salamone JD, Correa M (2002) Motivational views of reinforcement: implications for understanding the behavioral functions of nucleus accumbens dopamine. Behav Brain Res 137:3–25CrossRefPubMedGoogle Scholar
  56. Salamone JD, Steinpreis RE, McCullough LD, Smith P, Grebel D, Mahan K (1991) Haloperidol and nucleus accumbens dopamine depletion suppress lever pressing for food but increase free food consumption in a novel food choice procedure. Psychopharmacology 104:515–521. doi: 10.1007/BF02245659 CrossRefPubMedGoogle Scholar
  57. Salamone JD, Cousins MS, Bucher S (1994) Anhedonia or anergia? Effects of haloperidol and nucleus accumbens dopamine depletion on instrumental response selection in a T-maze cost/benefit procedure. Behav Brain Res 65:221–229. doi: 10.1016/0166-4328(94)90108-2 CrossRefPubMedGoogle Scholar
  58. Salamone JD, Cousins MS, Maio C, Champion M, Turski T, Kovach J (1996) Different behavioral effects of haloperidol, clozapine and thioridazine in a concurrent lever pressing and feeding procedure. Psychopharmacology 125:105–112. doi: 10.1007/BF02249408 CrossRefPubMedGoogle Scholar
  59. 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. doi: 10.1016/S0149-7634(96)00017-6 CrossRefPubMedGoogle Scholar
  60. Salamone JD, Arizzi M, Sandoval MD, Cervone KM, Aberman JE (2002) Dopamine antagonists alter response allocation but do not suppress appetite for food in rats: contrast between the effects of SKF 83566, raclopride and fenfluramine on a concurrent choice task. Psychopharmacology 160:371–380. doi: 10.1007/s00213-001-0994-x CrossRefPubMedGoogle Scholar
  61. Salamone JD, Correa M, Mingote S, Weber S (2003) Accumbens dopamine and the regulation of effort in food-seeking behavior: implications for studies of natural motivation and psychiatry. J Pharmacol Exp Ther 305:1–8. doi: 10.1124/jpet.102.035063 CrossRefPubMedGoogle Scholar
  62. 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. doi: 10.1016/j.coph.2004.09.004 CrossRefPubMedGoogle Scholar
  63. Salamone JD, Correa M, Mingote SM, Weber SM, Farrar AM (2006) Nucleus accumbens dopamine and the forebrain circuitry involved in behavioral activation and effort-related decision making: implications for understanding anergia and psychomotor slowing in depression. Curr Psychiatry Rev 2:267–280. doi: 10.2174/157340006776875914 CrossRefGoogle Scholar
  64. Salamone JD, Correa M, Farrar A, Mingote SM (2007) Effort-related functions of nucleus accumbens dopamine and associated forebrain circuits. Psychopharmacology 191:461–482. doi: 10.1007/s00213-006-0668-9 CrossRefPubMedGoogle Scholar
  65. Salamone JD, Betz AJ, Ishiwari K, Felsted J, Madson L, Mirante B, Clark K, Font L, Korbey S, Sager TN, Hockemeyer J, Muller CE (2008a) Tremorolytic effects of adenosine A2A antagonists: implications for parkinsonism. Front Biosci 13:3594–3605CrossRefPubMedGoogle Scholar
  66. Salamone JD, Ishiwari K, Betz AJ, Farrar AM, Mingote SM, Font L, Hockemeyer J, Müller CE, Correa M (2008b) Dopamine/adenosine interactions related to locomotion and tremor in animal models: Possible relevance to parkinsonism. Parkinsonism Relat Disord 14:S130–S134CrossRefPubMedGoogle Scholar
  67. Schiffmann SN, Jacobs O, Vanderhaeghen JJ (1991) Striatal restricted adenosine A2A receptor (RDC8) is expressed by enkephalin but not by substance P neurons: an in situ hybridization histochemistry study. J Neurochem 57:1062–1071. doi: 10.1111/j.1471-4159.1991.tb08257.x CrossRefPubMedGoogle Scholar
  68. Schweimer J, Hauber W (2006) Involvement of the rat anterior cingulate cortex in control of instrumental responses guided by reward expectancy. Learn Mem 12:334–342. doi: 10.1101/lm.90605 CrossRefGoogle Scholar
  69. Schweimer J, Saft S, Hauber W (2005) Involvement of catecholamine neurotransmission in the rat anterior cingulate in effort-related decision making. Behav Neurosci 119:1687–1692. doi: 10.1037/0735-7044.119.6.1687 CrossRefPubMedGoogle Scholar
  70. Sink KS, Vemuri VK, Olszewska T, Makriyannis A, Salamone JD (2008) Cannabinoid CB1 antagonists and dopamine antagonists produce different effects on a task involving response allocation and effort-related choice in food-seeking behavior. Psychopharmacology 196:565–574. doi: 10.1007/s00213-007-0988-4 CrossRefPubMedGoogle Scholar
  71. Sokolowski JD, Salamone JD (1998) The role of nucleus accumbens dopamine in lever pressing and response allocation: effects of 6-OHDA injected into core and dorsomedial shell. Pharmacol Biochem Behav 59:557–566. doi: 10.1016/S0091-3057(97)00544-3 CrossRefPubMedGoogle Scholar
  72. Stahl SM (2002) The psychopharmacology of energy and fatigue. J Clin Psychiatry 63:7–8PubMedGoogle Scholar
  73. Svenningsson P, Le Moine C, Fisone G, Fredholm BB (1999) Distribution, biochemistry and function of striatal adenosine A2A receptors. Prog Neurobiol 59:355–396. doi: 10.1016/S0301-0082(99)00011-8 CrossRefPubMedGoogle Scholar
  74. Takahashi RN, Pamplona FA, Prediger RD (2008) Adenosine receptor antagonists for cognitive dysfunction: a review of animal studies. Front Biosci 13:2614–2632CrossRefPubMedGoogle Scholar
  75. Tylee A, Gastpar M, Lepine JP, Mendlewicz J (1999) DEPRES II (Depression Research in European Society II): a patient survey of the symptoms, disability and current management of depression in the community. Int Clin Psychopharmacol 14:139–151. doi: 10.1097/00004850-199905002-00001 CrossRefPubMedGoogle Scholar
  76. Van den Bos R, van der Harst J, Jonkman S, Schilders M, Spruijt B (2006) Rats assess costs and benefits according to an internal standard. Behav Brain Res 171:350–354. doi: 10.1016/j.bbr.2006.03.035 CrossRefPubMedGoogle Scholar
  77. Walton ME, Bannerman DM, Rushworth MF (2002) The role of rat medial frontal cortex in effort-based decision making. J Neurosci 22:10996–11003PubMedGoogle Scholar
  78. Walton ME, Bannerman DM, Alterescu K, Rushworth MF (2003) Functional specialization within medial frontal cortex of the anterior cingulate for evaluating effort-related decisions. J Neurosci 23:6475–6479PubMedGoogle Scholar
  79. Walton ME, Kennerley SW, Bannerman DM, Phillips PE, Rushworth MF (2006) Weighing up the benefits of work: behavioral and neural analyses of effort-related decision making. Neural Netw 19:1302–1314. doi: 10.1016/j.neunet.2006.03.005 CrossRefPubMedGoogle Scholar
  80. Wardas J, Konieczny J, Lorenc-Koci E (2001) SCH 58261, an A2A adenosine receptor antagonist, counteracts parkinsonian-like muscle rigidity in rats. Synapse 41:160–171. doi: 10.1002/syn.1070 CrossRefPubMedGoogle Scholar
  81. Yurgelun-Todd DA, Sava S, Dahlgren MK (2007) Mood disorders. Neuroimaging Clin N Am 17:511–521. doi: 10.1016/j.nic.2007.08.001 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Lila T. Worden
    • 1
    • 2
  • Mona Shahriari
    • 1
    • 3
  • Andrew M. Farrar
    • 1
  • Kelly S. Sink
    • 1
  • Jörg Hockemeyer
    • 4
  • Christa E. Müller
    • 4
  • John D. Salamone
    • 1
  1. 1.Division of Behavioral Neuroscience, Department of PsychologyUniversity of ConnecticutStorrsUSA
  2. 2.National Institute of Drug Abuse, National Institutes of HealthBethesdaUSA
  3. 3.University of Connecticut Health CenterFarmingtonUSA
  4. 4.Pharmazeutisches Institut, Pharmazeutische Chemie IUniversität BonnBonnGermany

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