Skip to main content
SpringerLink
Log in

The Role of Adenosine in the Ventral Striatal Circuits Regulating Behavioral Activation and Effort-Related Decision Making: Importance for Normal and Pathological Aspects of Motivation

  • Chapter
  • First Online:
Adenosine

Abstract

Motivated behavior can be characterized by a high degree of activity, vigor, and persistence. Brain dopamine (DA), particularly in the nucleus accumbens, has been implicated in activational aspects of motivation and effort-related processes. Accumbens DA depletions reduce the tendency of rats to work for food, and alter effort-related decision making, but leave aspects of food motivation such as appetite intact. Recent evidence indicates that the purine neuromodulator adenosine, largely through actions on adenosine A2A receptors, also participates in regulating effort-related processes. Intra-accumbens injections of adenosine A2A agonists produce effects that are similar to those produced by accumbens DA depletion or antagonism. Furthermore, systemic or intra-accumbens injections of adenosine A2A receptor antagonists can reverse the effects of DA D2 antagonists on effort-related choice behavior. In contrast, adenosine A1 receptor antagonists fail to reverse these motivational effects of DA D2 antagonism. These studies have implications for understanding the potential role of adenosine in the development and treatment of energy-related motivational symptoms such as anergia and fatigue in depression and other disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Aberman JE, Ward SJ, Salamone JD (1998) Effects of dopamine antagonists and accumbens dopamine depletions on time-constrained progressive-ratio performance. Pharmacol Biochem Behav 61:341–348

    Article  CAS  PubMed  Google Scholar 

  • Antoniou K, Papadopoulou-Daifoti Z, Hyphantis T, Papathanasiou G, Bekris E, Marselos M, Panlilio L, Müller CE, Goldberg SR, Ferré S (2005) A detailed behavioral analysis of the acute motor effects of caffeine in the rat: involvement of adenosine A1 and A2A receptors. Psychopharmacology (Berl) 183:154–162

    Article  CAS  Google Scholar 

  • Azdad K, Gall D, Woods AS, Ledent C, Ferré S, Schiffmann SN (2009) Dopamine D2 and adenosine A2A receptors regulate NMDA-mediated excitation in accumbens neurons through A2A-D2 receptor heteromerization. Neuropsychopharmacology 34:972–986

    Article  CAS  PubMed  Google Scholar 

  • Bardgett ME, Depenbrock M, Downs N, Points M, Green L (2009) Dopamine modulates effort-based decision making in rats. Behav Neurosci 123:463–467

    Article  CAS  Google Scholar 

  • Barraco RA, Martens KA, Parizon M, Normile HJ (1993) Adenosine A2a receptors in the nucleus accumbens mediate locomotor depression. Brain Res Bull 31:397–404

    Article  CAS  PubMed  Google Scholar 

  • Betz AJ, Vontell R, Valenta J, Worden L, Sink KS, Font L, Correa M, Sager TN, Salamone JD (2009) Effects of the adenosine A2A antagonist KW-6002 (istradefylline) on pimozide-induced oral tremor and striatal c-Fos expression: comparisons with the muscarinic antagonist tropicamide. Neuroscience 163:97–108

    Article  CAS  PubMed  Google Scholar 

  • Brody AL, Saxena S, Mandelkern MA, Fairbanks LA, Ho ML, Baxter LR (2001) Brain metabolic changes associated with symptom factor improvement in major depressive disorder. Biol Psychiatry 50:171–178

    Article  CAS  PubMed  Google Scholar 

  • Brown AS, Gershon S (1993) Dopamine and depression. J Neural Transm Gen Sect 91:75–109

    Article  CAS  PubMed  Google Scholar 

  • Caligiuri MP, Ellwanger J (2000) Motor and cognitive aspects of motor retardation in depression. J Affect Disord 57:83–93

    Article  CAS  PubMed  Google Scholar 

  • Collins LE, Galtieri DJ, Collins P, Jones SK, Port RG, Paul NE, Hockemeyer J, Müller CE, Salamone JD (2010) Interactions between adenosine and dopamine receptor antagonists with different selectivity profiles: effects on locomotor activity. Behav Brain Res 211:148–155

    Article  CAS  PubMed  Google Scholar 

  • Correa M, Font L (2008) Is there a major role for adenosine A2A receptors in anxiety? Front Biosci 13:4058–4070

    Article  CAS  PubMed  Google Scholar 

  • Correa M, Carlson BB, Wisniecki A, Salamone JD (2002) Nucleus accumbens dopamine and work requirements on interval schedules. Behav Brain Res 137:179–187

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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 46:943–951

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Cunha RA, Ferré S, Vaugeois JM, Chen JF (2008) Potential therapeutic interest of adenosine A2A receptors in psychiatric disorders. Curr Pharm Des 14:1512–1524

    Article  CAS  PubMed  Google Scholar 

  • Daly JW, Fredholm BB (1998) Caffeine-an atypical drug of dependence. Drug Alcohol Depend 51:199–206

    Article  CAS  PubMed  Google Scholar 

  • Davis TR, Kensler CJ, Dews PB (1973) Comparison of behavioral effects of nicotine, d-amphetamine, caffeine and dimethylheptyl tetrahydrocannabinol in squirrel monkeys. Psychopharmacology (Berl) 32:51–65

    Article  CAS  Google Scholar 

  • DeMet EM, Chicz-DeMet A (2002) Localization of adenosine A2A-receptors in rat brain with [3 H]ZM-241385. Naunyn Schmiedebergs Arch Pharmacol 366:478–481

    Article  CAS  PubMed  Google Scholar 

  • Demyttenaere K, De Fruyt J, Stahl SM (2005) The many faces of fatigue in major depressive disorder. Int J Neuropsychopharmacol 8:93–105

    Article  PubMed  Google Scholar 

  • 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 (Berl) 179:587–596

    Article  CAS  Google Scholar 

  • Dess NK (2000) Responses to basic taste qualities in rats selectively bred for high versus low saccharin intake. Physiol Behav 69:247–257

    Article  CAS  PubMed  Google Scholar 

  • Dews PB (1955) Studies on behavior. I. Differential sensitivity to pentobarbital of pecking performance in pigeons depending on the schedule of reward. J Pharmacol Exp Ther 113:393–401

    CAS  PubMed  Google Scholar 

  • Dews PB (1958) Studies on behavior. IV. Stimulant actions of methamphetamine. J Pharmacol Exp Ther 122:137–147

    CAS  PubMed  Google Scholar 

  • Diller JW, Saunders BT, Anderson KG (2008) Effects of acute and repeated administration of caffeine on temporal discounting in rats. Pharmacol Biochem Behav 89:546–555

    Article  CAS  PubMed  Google Scholar 

  • El Yacoubi M, Ledent C, Parmentier M, Bertorelli R, Ongini E, Costentin J, Vaugeois JM (2001) Adenosine A2A receptor antagonists are potential antidepressants: evidence based on pharmacology and A2A receptor knockout mice. Br J Pharmacol 134:68–77

    Article  CAS  PubMed  Google Scholar 

  • El Yacoubi M, Costentin J, Vaugeois JM (2003) Adenosine A2A receptors and depression. Neurology 61(S6):S82–S87

    Article  CAS  PubMed  Google Scholar 

  • Elbers R, van Wegen EEH, Rochester R, Hetherington V, Nieuwboer A, Willems AM, Jones D, Kwakkel G (2009) Is impact of fatigue an independent factor associated with physical activity in idiopathic Parkinson’s disease. Mov Disord 24:1512–1518

    Article  PubMed  Google Scholar 

  • Farrar AM, Pereira M, Velasco F, Hockemeyer J, Müller 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 (Berl) 191:579–586

    Article  CAS  Google Scholar 

  • 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 152:321–330

    Article  CAS  PubMed  Google Scholar 

  • Farrar AM, Segovia KN, Randall PA, Nunes EJ, Collins LE, Stopper CM, Port RG, Hockemeyer J, Müller CE, Correa M, Salamone JD (2010) Nucleus accumbens and effort-related functions: behavioral and neural markers of the interactions between adenosine A2A and dopamine D2 receptors. Neuroscience 166:1056–1067

    Article  CAS  PubMed  Google Scholar 

  • Ferré S (1997) Adenosine-dopamine interactions in the ventral striatum. Implications for the treatment of schizophrenia. Psychopharmacology (Berl) 133:107–120

    Article  Google Scholar 

  • Ferré S (2008) An update on the mechanisms of the psychostimulant effects of caffeine. J Neurochem 105:1067–1079

    Article  PubMed  CAS  Google Scholar 

  • Ferré S, Popoli P, Gimenez-Llort L, Rimondini R, Muller CE, Stromberg I, Ogren SO, Fuxe K (2001) Adenosine/dopamine interaction: implications for the treatment of Parkinson’s disease. Parkinsonism Relat Disord 7:235–241

    Article  PubMed  Google Scholar 

  • Ferré S, Ciruela F, Canals M, Marcellino D, Burgueno J, Casado V, Hillion J, Torvinen M, Fanelli F, Benedetti PP, 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

    Article  PubMed  Google Scholar 

  • Ferré S, Ciruela F, Borycz J, Solinas M, Quarta D, Antoniou K, Quiroz C, Justinova Z, Lluis C, Franco R, Goldberg SR (2008a) Adenosine A1-A2A receptor heteromers: new targets for caffeine in the brain. Front Biosci 13:2391–2399

    Article  PubMed  Google Scholar 

  • Ferré S, Quiroz C, Woods AS, Cunha R, Popoli P, Ciruela F, Lluis C, Franco R, Azdad K, Schiffmann SN (2008b) An update on adenosine A2A-dopamine D2 receptor interactions: implications for the function of G protein-coupled receptors. Curr Pharm Des 14:1468–1474

    Article  PubMed  Google Scholar 

  • Fink JS, Weaver DR, Rivkees SA, Peterfreund RA, Pollack AE, Adler EM, Reppert SM (1992) Molecular cloning of the rat A2 adenosine receptor: selective co-expression with D2 dopamine receptors in rat striatum. Brain Res Mol Brain Res 14:186–195

    Article  CAS  PubMed  Google Scholar 

  • Floresco SB, Ghods-Sharifi S (2007) Amygdala-prefrontal cortical circuitry regulates effort-based decision making. Cereb Cortex 17:251–260

    Article  PubMed  Google Scholar 

  • Floresco SB, Tse MT, Ghods-Sharifi S (2008) Dopaminergic and glutamatergic regulation of effort- and delay-based decision making. Neuropsychopharmacology 33:1966–1979

    Article  CAS  PubMed  Google Scholar 

  • Font L, Mingote S, Farrar AM, Pereira M, Worden L, Stopper C, Port RG, Salamone JD (2008) Intra-accumbens injections of the adenosine A2A agonist CGS 21680 affect effort-related choice behavior in rats. Psychopharmacology (Berl) 199:515–526

    Article  CAS  Google Scholar 

  • Friedman JH, Brown RG, Comella C, Garber CE, Krupp LB, Lou JS, Marsh L, Nail L, Shulman L, Taylor CB (2007) Fatigue in Parkinson’s disease: a review. Mov Disord 22:297–308

    Article  PubMed  Google Scholar 

  • 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–S23

    Article  CAS  PubMed  Google Scholar 

  • 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 92:210–217

    Article  CAS  PubMed  Google Scholar 

  • Garrett BE, Holtzman SG (1994) D1 and D2 dopamine receptor antagonists block caffeine-induced stimulation of locomotor activity in rats. Pharmacol Biochem Behav 47:89–94

    Article  CAS  PubMed  Google Scholar 

  • Hanff TC, Furst SJ, Minor TR (2010) Biochemical and anatomical substrates of depression and sickness behavior. Isr J Psychiatry Relat Sci 47:64–71

    PubMed  Google Scholar 

  • Harris RA, Snell D, Loh HH (1978) Effects of d-amphetamine, monomethoxyamphetamines and hallucinogens on schedule-controlled behavior. J Pharmacol Exp Ther 204:103–117

    CAS  PubMed  Google Scholar 

  • Hauber W, Sommer S (2009) Prefrontostriatal circuitry regulates effort-related decision making. Cereb Cortex 19:2240–2247

    Article  PubMed  Google Scholar 

  • Hickie I, Ward P, Scott E, Haindl W, Walker B, Dixon J, Turner K (1999) Neo-striatal rCBF correlates of psychomotor slowing in patients with major depression. Psychiatry Res 92:75–81

    Article  CAS  PubMed  Google Scholar 

  • 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, Ferre S, Fuxe K (2002) Coaggregation, cointernalization, and codesensitization of adenosine A2A receptors and dopamine D2 receptors. J Biol Chem 277:18091–18097

    Article  CAS  PubMed  Google Scholar 

  • Hodgson RA, Bertorelli R, Varty GB, Lachowicz JE, Forlani A, Fredduzzi S, Cohen-Williams ME, Higgins GA, Impagnatiello F, Nicolussi E, Parra LE, Foster C, Zhai Y, Neustadt BR, Stamford AW, Parker EM, Reggiani A, Hunter JC (2009) Characterization of the potent and highly selective A2A receptor antagonists preladenant and SCH 412348 [7-[2-[4-2,4-difluorophenyl]-1-piperazinyl]ethyl]-2-(2-furanyl)-7 H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine] in rodent models of movement disorders and depression. J Pharmacol Exp Ther 330:294–303

    Article  CAS  PubMed  Google Scholar 

  • Ishiwari K, Weber SM, Mingote S, Correa M, Salamone JD (2004) Accumbens dopamine and the regulation of effort in food-seeking behavior: modulation of work output by different ratio or force requirements. Behav Brain Res 151:83–91

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Jenner P (2005) Istradefylline, a novel adenosine A2A receptor antagonist, for the treatment of Parkinson’s disease. Expert Opin Investig Drugs 14:729–738

    Article  CAS  PubMed  Google Scholar 

  • Justinova Z, Ferre S, Segal PN, Antoniou K, Solinas M, Pappas LA, Highkin JL, Hockemeyer J, Munzar P, Goldberg SR (2003) Involvement of adenosine A1 and A2A receptors in the adenosinergic modulation of the discriminative-stimulus effects of cocaine and methamphetamine in rats. J Pharmacol Exp Ther 307:977–986

    Article  CAS  PubMed  Google Scholar 

  • Justinova Z, Ferré S, Barnes C, Wertheim CE, Pappas LA, Goldberg SR, Le Foll B (2009) Effects of chronic caffeine exposure on adenosinergic modulation of the discriminative-stimulus effects of nicotine, methamphetamine, and cocaine in rats. Psychopharmacology (Berl) 203:355–367

    Article  CAS  Google Scholar 

  • Karcz-Kubicha M, Antoniou K, Terasmaa A, Quarta D, Solinas M, Justinova Z, Pezzola A, Reggio R, Müller CE, Fuxe K, Goldberg SR, Popoli P, Ferré S (2003) Involvement of adenosine A1 and A2A receptors in the motor effects of caffeine after its acute and chronic administration. Neuropsychopharmacology 28:1281–1291

    Article  CAS  PubMed  Google Scholar 

  • Koch M, Schmid A, Schnitzler HU (2000) Role of nucleus accumbens dopamine D1 and D2 receptors in instrumental and Pavlovian paradigms of conditioned reward. Psychopharmacology (Berl) 152:67–73

    Article  CAS  Google Scholar 

  • Koob GF, Riley SJ, Smith SC, Robbins TW (1978) Effects of 6-hydroxydopamine lesions of the nucleus accumbens septi and olfactory tubercle on feeding, locomotor activity, and amphetamine anorexia in the rat. J Comp Physiol Psychol 92:917–927

    Article  CAS  PubMed  Google Scholar 

  • Lopez-Cruz L, Pardo M, Dosda A, Salamone JD, Correa M (2011) Comparison between high doses of caffeine and theophylline on motor and anxiogenic effects in CD1 mice: studies of acute and chronic administration. Behav Pharmacol 22:e71–e72

    Article  CAS  Google Scholar 

  • Marston HM, Finlayson K, Maemoto T, Olverman HJ, Akahane A, Sharkey J, Butcher SP (1998) Pharmacological characterization of a simple behavioral response mediated selectively by central adenosine A1 receptors, using in vivo and in vitro techniques. J Pharmacol Exp Ther 285:1023–1030

    CAS  PubMed  Google Scholar 

  • McCullough LD, Salamone JD (1992) Involvement of nucleus accumbens dopamine in the motor activity induced by periodic food presentation: a microdialysis and behavioral study. Brain Res 592:29–36

    Article  CAS  PubMed  Google Scholar 

  • McKim WA (1980) The effect of caffeine, theophylline and amphetamine on operant responding of the mouse. Psychopharmacology (Berl) 68:135–138

    Article  CAS  Google Scholar 

  • 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 21:1749–1757

    Article  PubMed  Google Scholar 

  • 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 28:9037–9046

    Article  CAS  PubMed  Google Scholar 

  • Minor TR, Huang Q, Foley EA (2003) Cytokine-purine interactions in behavioral depression in rats. Integr Physiol Behav Sci 38:189–202

    Article  PubMed  Google Scholar 

  • Minor TR, Huang Q, Witt AE (2006) Cytokine-purine interactions in traumatic stress, behavioral depression, and sickness. CNS Neurol Disord Drug Targets 5:547–560

    Article  PubMed  Google Scholar 

  • 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

    Article  Google Scholar 

  • Mott AM, Nunes EJ, Collins LE, Port RG, Sink KS, Hockemeyer J, Müller CE, Salamone JD (2009) The adenosine A2A antagonist MSX-3 reverses the effects of the dopamine antagonist haloperidol on effort-related decision making in a T-maze cost/benefit procedure. Psychopharmacology (Berl) 204:103–112

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Nunes EJ, Randall PA, Santerre JL, Given AB, Sager TN, Correa M, Salamone JD (2010) Differential effects of selective adenosine antagonists on the effort-related impairments induced by dopamine D1 and D2 antagonism. Neuroscience 170:268–280

    Article  CAS  PubMed  Google Scholar 

  • Pardo M, Lopez-Cruz L, Hockemeyer J, Müller CE, Salamone JD, Correa M (2010) Interaction between dopamine D2 receptor and adenosine A1 and A2A receptors: studies of c-Fos immunoreactivity, behavioral activation and effort related decision making. Program No. 916.19. 2010. Neuroscience Meeting Planner, Society for Neuroscience, 2010, San Diego, CA. Online

    Google Scholar 

  • Pardo M, Randall PA, Nunes E, Lopez-Cruz L, Correa M, Salamone JD (2011) A progressive ratio/chow feeding concurrent choice task as a measure of effort-related decision making: effects of dopamine and adenosine antagonism. Behav Pharmacol 22:e58

    Article  CAS  Google Scholar 

  • Pardo M, Lopez-Cruz L, Valverde O, Ledent C, Baqi Y, Müller CE, Salamone JD, Correa M (2012) Adenosine A2A receptor antagonism and genetic deletion attenuate the effects of dopamine D2 antagonism on effort-based decision making in mice. Neuropharmacology 62(5–6):2068–2077

    Article  CAS  PubMed  Google Scholar 

  • Pinna A (2010) Novel investigational adenosine A2A receptor antagonists for Parkinson’s disease. Expert Opin Investig Drugs 18:1619–1631

    Article  CAS  Google Scholar 

  • Popoli P, Reggio R, Pèzzola A, Fuxe K, Ferré S (1998) Adenosine A1 and A2A receptor antagonists stimulate motor activity: evidence for an increased effectiveness in aged rats. Neurosci Lett 251:201–204

    Article  CAS  PubMed  Google Scholar 

  • Rampello L, Nicoletti G, Raffaele R (1991) Dopaminergic hypothesis for retarded depression: a symptom profile for predicting therapeutical responses. Acta Psychiatr Scand 84:552–554

    Article  CAS  PubMed  Google Scholar 

  • Randall PA, Nunes EJ, Janniere SL, Stopper CM, Farrar AM, Sager TN, Baqi Y, Hockemeyer J, Müller CE, Salamone JD (2011a) Stimulant effects of adenosine antagonists on operant behavior: differential actions of selective A2A and A1 antagonists. Psychopharmacology (Berl) 216:173–186

    Article  CAS  Google Scholar 

  • Randall PA, Pardo M, Nunes EJ, Lopez-Cruz L, Blodgett A, Lingiah K, Leser C, Vemuri VK, Mackriyannis A, Baqi Y, Müller CE, Correa M, Salamone JD (2011b) Effort-related choice behavior as assessed by a progressive ratio/chow feeding task: differential effects of DA D2 antagonism, adenosine A2A antagonism, cannabinoid CB1 antagonism and pre-feeding. Program No. 732.03. 2011. Neuroscience Meeting Planner. Society for Neuroscience, 2011, Washington, DC. Online

    Google Scholar 

  • Robbins TW, Everitt BJ (2007) A role for mesencephalic dopamine in activation: a commentary on Berridge (2007). Psychopharmacology (Berl) 191:433–437

    Article  CAS  Google Scholar 

  • Robbins TW, Koob GF (1980) Selective disruption of displacement behaviour by lesions of the mesolimbic dopamine system. Nature 285:409–412

    Article  CAS  PubMed  Google Scholar 

  • Rogers D, Lees AJ, Smith E, Trimble M, Stern GM (1987) Bradyphrenia in Parkinson’s disease and psychomotor retardation in depressive illness. An experimental study. Brain 110:761–776

    Article  PubMed  Google Scholar 

  • Salamone JD (1988) Dopaminergic involvement in activational aspects of motivation: effects of haloperidol on schedule induced activity, feeding and foraging in rats. Psychobiology 16:196–206

    CAS  Google Scholar 

  • 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, pp 599–613

    Google Scholar 

  • Salamone JD (1992) Complex motor and sensorimotor functions of striatal and accumbens dopamine: involvement in instrumental behavior processes. Psychopharmacology (Berl) 107:160–174

    Article  CAS  Google Scholar 

  • Salamone JD (2010) Preladenant, a novel adenosine A(2A) receptor antagonist for the potential treatment of parkinsonism and other disorders. IDrugs 13:723–731

    CAS  PubMed  Google Scholar 

  • Salamone JD, Correa M (2002) Motivational views of reinforcement: implications for understanding the behavioral functions of nucleus accumbens dopamine. Behav Brain Res 137:3–25

    Article  CAS  PubMed  Google Scholar 

  • Salamone JD, Correa M (2009) Dopamine/adenosine interactions involved in effort-related aspects of food motivation. Appetite 53:422–425

    Article  CAS  PubMed  Google Scholar 

  • 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 (Berl) 104:515–521

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Salamone JD, Wisniecki A, Carlson BB, Correa M (2001) Nucleus accumbens dopamine depletions make animals highly sensitive to high fixed ratio requirements but do not impair primary food reinforcement. Neuroscience 105:863–870

    Article  CAS  PubMed  Google Scholar 

  • 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 (Berl) 160:371–380

    Article  CAS  Google Scholar 

  • 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 of understanding anergia and psychomotor slowing and depression. Curr Psychiatry Rev 2:267–280

    Article  Google Scholar 

  • Salamone JD, Correa M, Farrar A, Mingote SM (2007) Effort-related functions of nucleus accumbens dopamine and associated forebrain circuits. Psychopharmacology (Berl) 191:461–482

    Article  CAS  Google Scholar 

  • Salamone JD, Betz AJ, Ishiwari K, Felsted J, Madson L, Mirante B, Clark K, Font L, Korbey S, Sager TN, Hockemeyer J, Muller CE (2008) Tremorolytic effects of adenosine A2A antagonists: implications for parkinsonism. Front Biosci 13:3594–3605

    Article  CAS  PubMed  Google Scholar 

  • Salamone JD, Correa M, Farrar AM, Nunes EJ, Pardo M (2009a) Dopamine, behavioral economics, and effort. Front Behav Neurosci 3:13

    Article  PubMed  CAS  Google Scholar 

  • Salamone JD, Farrar AM, Font L, Patel V, Schlar DE, Nunes EJ, Collins LE, Sager TN (2009b) Differential actions of adenosine A1 and A2A antagonists on the effort-related effects of dopamine D2 antagonism. Behav Brain Res 201:216–222

    Article  CAS  PubMed  Google Scholar 

  • Sanger DJ, Blackman DE (1974) Rate-dependent effects of drugs: a review of the literature. Pharmacol Biochem Behav 4:73–83

    Article  Google Scholar 

  • Santerre JL, Nunes EJ, Kovner R, Leser C, Randall PA, Collins-Praino LE, Correa M, Baqi Y, Müller CE, Salamone JD (2012) The novel adenosine A2A antagonist prodrug MSX-4 is effective in animal models related to motivational and motor function. Pharmacol Biochem Behav, in press

    Article  Google Scholar 

  • Schiffmann SN, Jacobs O, Vanderhaeghen JJ (1991) Striatal restricted adenosine A2 receptor (RDC8) is expressed by enkephalin but not by substance P neurons: an in situ hybridization histochemistry study. J Neurochem 57:1062–1067

    Article  CAS  PubMed  Google Scholar 

  • Schmidt K, Nolte-Zenker B, Patzer J, Bauer M, Schmidt LG, Heinz A (2001) Psychopathological correlates of reduced dopamine receptor sensitivity in depression, schizophrenia, and opiate and alcohol dependence. Pharmacopsychiatry 34:66–72

    Article  CAS  PubMed  Google Scholar 

  • Schweimer J, Hauber W (2005a) Involvement of the rat anterior cingulate cortex in control of instrumental responses guided by reward expectancy. Learn Mem 12:334–342

    Article  PubMed  Google Scholar 

  • Schweimer J, Hauber W (2005b) Dopamine D1 receptors in the anterior cingulate cortex regulate effort-based decision making. Learn Mem 13:777–782

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Simola N, Fenu S, Baraldi PG, Tabrizi MA, Morelli M (2004) Blockade of adenosine A2A receptors antagonizes parkinsonian tremor in the rat tacrine model by an action on specific striatal regions. Exp Neurol 189:182–188

    Article  CAS  PubMed  Google Scholar 

  • 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 (Berl) 196:565–574

    Article  CAS  Google Scholar 

  • Stahl SM (2002) The psychopharmacology of energy and fatigue. J Clin Psychiatry 63:7–8

    Article  PubMed  Google Scholar 

  • Svenningsson P, Le Moine C, Fisone G, Fredholm BB (1999) Distribution, biochemistry and function of striatal adenosine A2A receptors. Prog Neurobiol 59:355–396

    Article  CAS  PubMed  Google Scholar 

  • Takahashi RN, Pamplona FA, Prediger RD (2008) Adenosine receptor antagonists for cognitive dysfunction: a review of animal studies. Front Biosci 13:2614–2632

    Article  CAS  PubMed  Google Scholar 

  • Tellez N, Alonso J, Rio M, Tintore M, Nos C, Montalban X, Rovira A (2008) The basal ganglia: a substrate for fatigue in multiple sclerosis. Neuroradiology 50:17–23

    Article  CAS  PubMed  Google Scholar 

  • Treadway MT, Zald DH (2011) Reconsidering anhedonia in depression: lessons from translational neuroscience. Neurosci Biobehav Rev 35:537–555

    Article  PubMed  Google Scholar 

  • 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. DEPRES Steering Committee. Int Clin Psychopharmacol 14:139–151

    CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Volkow ND, Chang L, Wang GJ, Fowler JS, Leonido-Yee M, Franceschi D, Sedler MJ, Gatley SJ, Hitzemann R, Ding YS, Logan J, Wong C, Miller EN (2001) Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers. Am J Psychiatry 158:377–382

    Article  CAS  PubMed  Google Scholar 

  • Vontell R, Segovia KN, Betz AJ, Mingote S, Goldring K, Cartun RW, Salamone JD (2010) Immunocytochemistry studies of basal ganglia adenosine A2A receptors in rat and human tissue. J Histotechnol 33:41–47

    CAS  Google Scholar 

  • Wakabayashi KT, Fields HL, Nicola SM (2004) Dissociation of the role of nucleus accumbens dopamine in responding to reward-predictive cues and waiting for reward. Behav Brain Res 154:19–30

    Article  CAS  PubMed  Google Scholar 

  • Wallace M, Singer G, Finlay J, Gibson S (1983) The effect of 6-OHDA lesions of the nucleus accumbens septum on schedule-induced drinking, wheelrunning and corticosterone levels in the rat. Pharmacol Biochem Behav 18:129–136

    Article  CAS  PubMed  Google Scholar 

  • Walton ME, Bannerman DM, Rushworth MF (2002) The role of rat medial frontal cortex in effort-based decision making. J Neurosci 22:10996–11003

    CAS  PubMed  Google Scholar 

  • 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 23:6475–6479

    CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Wardas J, Konieczny J, Lorenc-Koci E (2001) SCH 58261, an A(2A) adenosine receptor antagonist, counteracts parkinsonian-like muscle rigidity in rats. Synapse 41:160–171

    Article  CAS  PubMed  Google Scholar 

  • Worden LT, Shahriari M, Farrar AM, Sink KS, Hockemeyer J, Muller CE, Salamone JD (2009) The adenosine A2A antagonist MSX-3 reverses the effort-related effects of dopamine blockade: differential interaction with D1 and D2 family antagonists. Psychopharmacology (Berl) 203:489–499

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant to J.D. Salamone from the National Institute of Mental Health (MH078023), and to M. Correa from Fundació Bancaixa-UJI (P1.1B2010-43), and Plan Nacional de Drogas, Ministerio de Política Social y Consumo (2010I024), Spain.

Financial and competing interests disclosure: For some studies reviewed in this manuscript, KW6002 was generously supplied by Lundbeck (Copenhagen, Denmark), and J.D. Salamone also has received a research grant from Pfizer and Merck.

Author information

Authors and Affiliations

  1. Division of Behavioral Neuroscience, Department of Psychology, University of Connecticut, Storrs, CT, 06269-1020, USA

    John D. Salamone Ph.D., Merce Correa, Patrick A. Randall & Eric J. Nunes

  2. Department of Psicobiology, Universitat Jaume I, Castelló, 12071, Spain

    Merce Correa, Marta Pardo & Laura Lopez-Cruz

Authors
  1. John D. Salamone Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Merce Correa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Patrick A. Randall
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eric J. Nunes
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marta Pardo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Laura Lopez-Cruz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John D. Salamone Ph.D. .

Editor information

Editors and Affiliations

  1. Trinity College, 300 Summit Street, LSC 208, Hartford, 06106, USA

    Susan Masino

  2. Legacy Research Institute, Portland, OR,, 1225 NE 2nd Avenue, Portland, 97232, USA

    Detlev Boison

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Salamone, J.D., Correa, M., Randall, P.A., Nunes, E.J., Pardo, M., Lopez-Cruz, L. (2013). The Role of Adenosine in the Ventral Striatal Circuits Regulating Behavioral Activation and Effort-Related Decision Making: Importance for Normal and Pathological Aspects of Motivation. In: Masino, S., Boison, D. (eds) Adenosine. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3903-5_23

Download citation

Publish with us

Policies and ethics

Search

Navigation