Skip to main content
Log in

Effort-related motivational effects of the pro-inflammatory cytokine interleukin 1-beta: studies with the concurrent fixed ratio 5/ chow feeding choice task

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Effort-related motivational symptoms such as anergia and fatigue are common in patients with depression and other disorders. Research implicates pro-inflammatory cytokines in depression, and administration of cytokines can induce effort-related motivational symptoms in humans.

Objectives

The present experiments focused on the effects of the pro-inflammatory cytokine interleukin 1-beta (IL-1β) on effort-related choice behavior.

Methods

Rats were tested on a concurrent fixed ratio 5 lever pressing/chow feeding choice procedure, which assesses the tendency of rats to work for a preferred food (high carbohydrate pellets) in the presence of a concurrently available but less preferred substitute (laboratory chow).

Results

IL-1β (1.0–4.0 μg/kg IP) shifted choice behavior, significantly decreasing lever pressing and increasing intake of the freely available chow. The second experiment assessed the ability of the adenosine A2A antagonist (E)-phosphoric acid mono-[3-[8-[2-(3-methoxyphenyl)vinyl]-7-methyl-2,6-dioxo-1-prop-2-ynyl-1,2,6,7-tetrahydropurin-3-yl] propyl] ester disodium salt (MSX-3) to reverse the behavioral effects of IL-1β. MSX-3 attenuated the effort-related impairments produced by IL-1β, increasing lever pressing and also decreasing chow intake. In the same dose range that shifted effort-related choice behavior, IL-1β did not alter food intake or preference in parallel free-feeding choice studies, indicating that these low doses were not generally suppressing appetite or altering preference for the high carbohydrate pellets. In addition, IL-1β did not affect core body temperature.

Conclusions

These results indicate that IL-1β can reduce the tendency to work for food, even at low doses that do not produce a general sickness, malaise, or loss of appetite. This research has implications for the involvement of cytokines in motivational symptoms such as anergia and fatigue.

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Aubert A, Kelley KW, Dantzer R (1997) Differential effect of lipopolysaccharide on food hoarding behavior and food consumption in rats. Brain Behav Immun 11(3):229–238

    Article  CAS  PubMed  Google Scholar 

  • Bret-Dibat JL, Bluthé RM, Kent S, Kelley KW, Dantzer R (1995) Lipopolysaccharide and interleukin-1 depress food motivated behavior in mice by a vagal-mediated mechanism. Brain Behav Immun 9(3):242–246

    Article  CAS  PubMed  Google Scholar 

  • Cagniard B, Balsam PD, Brunner D, Zhuang X (2006) Mice with chronically elevated dopamine exhibit enhanced motivation, but not learning, for a food reward. Neuropsychopharmacology 31:1362–1370

    Article  CAS  PubMed  Google Scholar 

  • Capuron L, Hauser P, Hinze-Selch D, Miller AH, Neveu PJ (2002) Treatment of cytokine-induced depression. Brain Behav Immun 16(5):575–580

    Article  CAS  PubMed  Google Scholar 

  • Capuron L, Fornwalt FB, Knight BT, Harvey PD, Ninan PT, Miller AH (2009) Does cytokine-induced depression differ from idiopathic major depression in medically healthy individuals? J Affect Disord 119:181–185

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Capuron L, Pagnoni G, Drake DF, Woolwine BJ, Spivey JR, Crowe RJ, Votaw JR, Goodman MM, Miller AH (2012) Dopaminergic mechanisms of reduced basal ganglia responses to hedonic reward during interferon alpha administration. Arch Gen Psychiatry 69(10):1044–1053

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Castanon N, Bluthé RM, Danzter R (2001) Chronic treatment with the atypical antidepressant tianeptine attenuates sickness behavior induced by peripheral but not central lipopolysaccharide and interleukin-1beta in the rat. Psychopharmacology (Berl) 154(1):50–60

    Article  CAS  Google Scholar 

  • Cattaneo A, Gennarelli M, Uher R, Breen G, Farmer A, Aitchison KJ, Craig IW, Anacker C, Zunsztain PA, McGuffin P, Pariante CM (2013) Candidate genes expression profile associated with antidepressants response in the GENDEP Study: differentiating between baseline ‘predictors’ and longitudinal ‘targets’. Neuropsychopharmacology 38:377–385

    Article  CAS  PubMed  Google Scholar 

  • Cousins MS, Wei W, Salamone JD (1994) Pharmacological characterization of performance on a concurrent lever pressing/feeding choice procedure: effects of dopamine antagonists, cholinomimetic, sedative and stimulant drugs. Psychopharmacology (Berl) 116(4):529–537

    Article  CAS  Google Scholar 

  • Cuthbert BN, Insel TR (2013) Toward the future of psychiatric diagnosis: the seven pillars of RDoC. BMC Med 11:126

    Article  PubMed Central  PubMed  Google Scholar 

  • Dantzer R (2001) Cytokine-induced sickness behavior: mechanisms and implications. Ann N Y Acad Sci 933:222–234

    Article  CAS  PubMed  Google Scholar 

  • Dantzer R, O’Connor JC, Freund GC, Johnson RW, Kelley KW (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 9:46–57

    Google Scholar 

  • Dantzer R (2009) Cytokine, sickness behavior, and depression. Immunol Allergy Clin North Am 29:247–264

    Article  PubMed Central  PubMed  Google Scholar 

  • Dantzer R, Meagher MW, Cleeland CS (2012) Translational approaches to treatment-induced symptoms in cancer patients. Nat Rev Clin Oncol 9:414–426

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dellagioia N, Devine L, Pittman B, Hannestad J (2013) Bupropion pre-treatment of endotoxin-induced depressive symptoms. Brain Behav Immun 31:197–204

    Article  CAS  PubMed  Google Scholar 

  • Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctôt KL (2010) A meta-analysis of cytokines in major depression. Biol Psychiatry 67(5):446–457

    Article  CAS  PubMed  Google Scholar 

  • Dunn AJ, Swiergiel AH (2005) Effects of interleukin-1 and endotoxin in the forced swim and tail suspension tests in mice. Pharmacol Biochem Behav 81(3):688–693

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • El Yacoubi M, Costentin J, Vaugeois JM (2003) Adenosine A2A receptors and depression. Neurology 61(Suppl 6):S82–S87

    Article  PubMed  Google Scholar 

  • 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 (Berl) 191:579–586

    Article  CAS  Google Scholar 

  • Farrar AM, Font L, Pereira M, Mingote S, Bunce JG, Chrobak JJ, Salamone JD (2008) Forebrain circuitry involved in effort-related choice: injections of the GABAA agonist muscimol into ventral pallidum alter response allocation in food-seeking behavior. Neuroscience 152:321–330

    Article  CAS  PubMed Central  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 

  • Felger JC, Miller AH (2012) Cytokine effects on the basal ganglia and dopamine function: the subcortical source of inflammatory malaise. Front Neuroendocrinol 33(3):315–327

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Felger JC, Cole SW, Pace TW, Hu F, Woolwine BJ, Doho GH, Raison CL, Miller AH (2012a) Molecular signatures of peripheral blood mononuclear cells during chronic interferon-α treatment: relationship with depression and fatigue. Psychol Med 42:1591–1603

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Felger JC, Li L, Marvar PJ, Woolwine BJ, Harrison DG, Raison CL, Miller AH (2012b) Tyrosine metabolism during interferon-alpha administration: association with fatigue and CSF dopamine concentrations. Brain Behav Immun 31:153–160

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Ferré S, Quiroz C, Woods AS, Cunha R, Popoli P, Ciruela F, Lluis C, Franco R, Azdad K, Schiffmann SN (2008) 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 Central  PubMed  Google Scholar 

  • Floresco SB, Ghods-Sharifi S (2007) Amygdala-prefrontal contrical circuitry regulates effort-based decision making. Cereb Cortex 17(2):251–260

    Article  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 

  • Frenois F, Moreau M, O'Connor J, Lawson M, Micon C, Lestage J, Kelley KW, Dantzer R, Castanon N (2007) Liopolysaccharide induces delayed FosB/DeltaFosB immunostaining within the mouse extended amygdala, hippocampus and hypothalamus, that parallel the expression of depressive-like behavior. Psychoneuroendocrinology 32:516–531

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gold JM, Strauss GP, Waltz JA, Robinson BM, Brown JK, Frank MJ (2013) Negative symptoms of schizophrenia are associated with abnormal effort-cost computations. Biol Psychiatry 74:130–136

    Article  PubMed  Google Scholar 

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

    Google Scholar 

  • Harboe E, Tjensvoll AB, Vefring HK, Goransson LG, Kvaloy JT, Omdal R (2009) Fatigue in primary Sjogren's syndrome—a link to sickness behaviour in animals? Brain Behav Immun 23:1103–1108

    Article  Google Scholar 

  • Harden LM, du Plessis I, Poole S, Laburn HP (2008) Interleukin (IL)-6 and IL-1 beta act synergistically within the brain to induce sickness behavior and fever in rats. Brain Behav Immun 22(6):838–849

    Article  CAS  PubMed  Google Scholar 

  • Hauber W, Sommer S (2009) Prefrontostriatal circuitry regulates effort-related decision making. Cereb Cortex 19(10):2240–2247

    Article  PubMed  Google Scholar 

  • Hiles SA, Baker AL, de Malmanche T, Attia J (2012) A meta-analysis of difference in IL-6 and IL-10 between people with and without depression: exploring the causes of heterogeneity. Brain Behav Immun 26(7):1180–1188

    Article  CAS  PubMed  Google Scholar 

  • Hockemeyer J, Burbiel JC, Müller 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 69:3308–3318

    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)-7H-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 

  • Kamata M, Higuchi H, Yoshimoto M, Yoshida K, Shimizu T (2000) Effect of single intracerebroventricular injection of alpha-interferon on monoamine concentrations in the rat brain. Eur Neuropsychopharmacol 10(2):129–132

    Article  CAS  PubMed  Google Scholar 

  • Katafuchi T, Kondo T, Take S, Yoshimura M (2005) Enhanced expression of brain interferon-alpha and serotonin transporter in immunologically induced fatigue in rats. Eur J Neurosci 22:2817–2826

    Article  PubMed  Google Scholar 

  • Katsarou Z, Bostantjopoulou S, Hatzizisi O, Giza E, Soler-Cardona A, Kyriazis G (2007) Immune factors or depression? Fatigue correlates in Parkinson's disease. Rev Neurol 45:725–728

    CAS  PubMed  Google Scholar 

  • Kent S, Bluthé RM, Kelley KW, Dantzer R (1992) Sickness behavior as a new target for drug development. Trends Pharmacol Sci 13:24–28

    Article  CAS  PubMed  Google Scholar 

  • Keppel G (1991) Design and analysis: a researcher's handbook, 3rd edn. Prentice-Hall, Englewood Cliffs, NJ

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

    Article  CAS  Google Scholar 

  • Lapierre Y, Hum S (2007) Treating fatigue. Internat MS J 14:64–71

    CAS  Google Scholar 

  • Larson SJ, Romanoff RL, Dunn AJ, Glowa JR (2002) Effects of interleukin-1beta on food-maintained behavior in the mouse. Brain Behav Immun 16(4):398–410

    Article  CAS  PubMed  Google Scholar 

  • Mai B, Sommer S, Hauber W (2012) Motivational states influence effort-based decision making in rats: the role of dopamine in the nucleus accumbens. Cogn Affect Behav Neurosci 12:74–84

    Article  PubMed  Google Scholar 

  • McLaughlin CL, Rogan GJ, Tou J, Baile CA, Joy WD (1992) Food intake and body temperature responses of rats to recombinant human interleukin-1 beta and a tripeptide interleukin-1 beta antagonist. Physiol Behav 52:1155–1160

    Article  CAS  PubMed  Google Scholar 

  • McLaughlin PJ, Lu D, Winston KM, Thakur G, Swezey LA, Makriyannis A, Salamone JD (2005) Behavioral effects of the novel cannabinoid full agonist AM 411. Pharmacol Biochem Behav 81:78–88

    Article  CAS  PubMed  Google Scholar 

  • McLaughlin PJ, Thakur GA, Vemuri VK, McClure ED, Brown CM, Winston KM, Wood JT, Makriyannis A, Salamone JD (2013) Behavioral effects of the novel potent cannabinoid CB1 agonist AM 4054. Pharmacol Biochem Behav 109:16–22

    Article  CAS  PubMed  Google Scholar 

  • Merali Z, Brennan K, Brau P, Anisman H (2003) Dissociating anorexia and anhedonis elicited by interleukin-1beta: anti-deprssant and gender effects on responding for “free chow” and “earned” sucrose intake. Psychopharmacology (Berl) 165(4):413–418

    CAS  Google Scholar 

  • Miller AH (2009) Mechanisms of cytokine-induced behavioral changes: psychoneuroimmunology at the translational interface. Brain Behav Immunity 23:149–158

    Article  CAS  Google Scholar 

  • Mingote S, Font L, Farrar AM, Vontell R, Worden LT, Stopper CM, Port RG, Sink KS, Bunce JG, Chrobak JJ, Salamone JD (2008a) Nucleus accumbens adenosine A2A receptors regulate exertion of effort by acting on the ventral striatopallidal pathway. J Neurosci 28:9037–9046

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mingote S, Pereira M, Farrar AM, McLaughlin PJ, Salamone JD (2008b) Systemic administration of the adenosine A(2A) agonist CGS 21680 induces sedation at doses that suppress lever pressing and food intake. Pharmacol Biochem Behav 89:345–351

    Article  CAS  PubMed Central  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 

  • 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(1):103–112

    Article  CAS  Google Scholar 

  • Mouihate A, Chen X, Pittman QJ (1998) Interleukin-1beta fever in rats: gender difference and estrous cycle influence. Am J Physiol 275(5 Pt 2):R1450–R1454

    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 Central  PubMed  Google Scholar 

  • Nunes EJ, Randall PA, Podurgiel S, Correa M, Salamone JD (2013) Nucleus accumbens neurotransmission and effort-related choice behavior in food motivation: effects of drugs acting on dopamine, adenosine, and muscarinic acetylcholine receptors. Neurosci Biobehav Rev, http://dx.doi.org/10.1016/j.neubiorev.2013.04.002

  • O'Connor JC, André C, Wang Y, Lawson MA, Szegedi SS, Lestage J, Castanon N, Kelley KW, Dantzer R (2009) Interferon-gamma and tumor necrosis factor-alpha mediate the upregulation of indoleamine 2,3-dioxygenase and the induction of depressive-like behavior in mice in response to bacillus Calmette–Guerin. J Neurosci 29:4200–4209

    Article  PubMed Central  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Raedler TJ (2011) Inflammatory mechanisms in major depressive disorder. Curr Opin Psychiatry 24(6):519–525

    PubMed  Google Scholar 

  • Raison CL, Capuron L, Miller AH (2006) Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol 27:24–31

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Randall PA, Pardo M, Nunes EJ, López Cruz L, Vemuri VK, Makriyannis A, Baqi Y, Mϋller CE, Correa M, Salamone JD (2012) Dopaminergic modulation of effort-related choice behavior as assessed by a progressive ratio chow feeding choice task: pharmacological studies and the role of individual differences. PLoS One 7(10):e47934

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rosin DL, Robeva A, Woodard RL, Guyenet PG, Linden J (1998) Immunohistochemical localization of adenosine A2A receptors in the rat central nervous system. J Comp Neurol 401:163–186

    Article  CAS  PubMed  Google Scholar 

  • Salamone JD, Correa M (2012) The mysterious motivational functions of mesolimbic dopamine. Neuron 76(3):470–485

    Article  CAS  PubMed  Google Scholar 

  • Salamone JD, Steinpreis RE, McCullough LD, Smith P, Grebel D, Mahan K (1991) Haloperidol and nucleus accumbens (DA) 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, 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 ration requirements but do not impair primary food reinforcement. Neuroscience 105(4):863–870

    Article  CAS  PubMed  Google Scholar 

  • Salamone JD, Arizzi MN, Sandoval MD, Cervone KM, Aberman JE (2002) (DA) 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 (DA) and the forebrain circuitry involved in behavioral activation and effort-related decision making: implications for understanding anergia and psychomotor slowing in depression. Curr Psychiat 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, Farrar AM, Font L, Patel V, Schlar DE, Nunes EJ, Collins LE, Sager TN (2009) Differential actions of adenosine A1 and A2A antagonists on the effort-related effects of (DA) D2 antagonism. Behav Brain Res 201:216–222

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Salamone JD, Correa M, Nunes EJ, Randall PA, Pardo M (2012) The behavioral pharmacology of effort-related choice behavior: dopamine, adenosine, and beyond. J Exp Anal Behav 97(1):125–146

    Article  PubMed  Google Scholar 

  • Santerre JL, Nunes EJ, Randall PA, Baqi Y, Müller CE, Salamone JD (2012) Behavioral studies with the novel adenosine A2A antagonist MSX-4: reversal of the effects of (DA) D2 antagonism. Pharamcol Biochem Behav 102(4):477–487

    Article  CAS  Google Scholar 

  • Segovia KN, Correa M, Salamone JD (2011) Slow phasic changes in nucleus accumbens dopamine release during fixed ratio acquisition: a microdialysis study. Neuroscience 196:178–188

    Article  CAS  PubMed  Google Scholar 

  • Segovia KN, Correa M, Lennington JB, Conover JC, Salamone JD (2012) Changes in nucleus accumbens and neostriatal c-Fos and DARPP-32 immunoreactivity during different stages of food-reinforced instrumental training. Eur J Neurosci 35(8):1354–1367

    Article  PubMed Central  PubMed  Google Scholar 

  • Shuto H, Kataoka Y, Korikawa T, Fujihara N, Oishi R (1997) Repeated interferon-alpha administration inhibits dopaminergic neural activity in the mouse brain. Brain Res 747(2): 348–351

    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(4):565–574

    Article  CAS  Google Scholar 

  • Song C, Li X, Kang Z, Kadotomi Y (2007) Omega-3 fatty acid ethyl-eicosapentaenoate attenuates IL-1beta-induced changes in dopamine and metabolites in the shell of the nucleus accumbens: involved with PLA2 activity and corticosterone secretion. Neuropsychopharmacology 32(2):736–744

    Article  CAS  PubMed  Google Scholar 

  • Song C, Manku MS, Horrobin DF (2008) Long-chain polyunsaturated fatty acids modulate interleukin-1beta-induced changes in behavior, monoaminergic neurotransmitters, and brain inflammation in rats. J Nutr 138(5):954–963

    CAS  PubMed  Google Scholar 

  • Taylor AN, Tio DL, Heng NS, Yirmiya R (2002) Alcohol consumption attenuates febrile responses to lipopolysaccharide and interleukin-1 beta in male rats. Alcohol Clin Exp Res 26:44–52

    CAS  PubMed  Google Scholar 

  • Treadway MT, Bossaller NA, Shelton RC, Zald DH (2012) Effort-based decision-making in major depressive disorder: a translational model of motivational anhedonia. J Abnorm Psychol 121(3):553–558

    Article  PubMed Central  PubMed  Google Scholar 

  • Walton ME, Bannerman DM, Alterescu K, Rushworth MFS (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 

  • Wardle MC, Treadway MT, Mayo LM, Zald DH, de Wit H (2011) Amping up effort: effects of d-amphetamine on human effort-based decision-making. J Neurosci 31(46):16597–16602

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Worden LT, Shahriari M, Farrar AM, Sink KS, Hockemeyer J, Müller 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(3):489–499

    Article  CAS  Google Scholar 

  • Wu TH, Lin CH (2008) IL-6 mediated alterations on immobile behavior of rats in the forced swim test via ERK1/2 activation in specific brain regions. Behav Brain Res 193:183–191

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant to J.S. from the National Institute of Mental Health (MH094966), and to Merce Correa from Fundació Bancaixa/U. Jaume I. (P1.1B2010-43), and a SURF grant to B. Epling.

Disclosure/conflict of interest

J. Salamone has received grants from Merck-Serrono, Pfizer, and Roche and is a consultant for Merz.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to John D. Salamone.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nunes, E.J., Randall, P.A., Estrada, A. et al. Effort-related motivational effects of the pro-inflammatory cytokine interleukin 1-beta: studies with the concurrent fixed ratio 5/ chow feeding choice task. Psychopharmacology 231, 727–736 (2014). https://doi.org/10.1007/s00213-013-3285-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-013-3285-4

Keywords

Navigation