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Effort-related motivational effects of the pro-inflammatory cytokine interleukin-6: pharmacological and neurochemical characterization

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Abstract

Rationale

Motivational dysfunctions such as anergia, fatigue, and reduced effort expenditure are common in patients with depression and other disorders. Pro-inflammatory cytokines are implicated in depression, and cytokine administration induces motivational deficits in humans.

Objectives

These studies focused on the effects of the cytokine interleukin-6 (IL-6) on effort-related decision-making.

Methods

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

Results

IL-6 (2.0–8.0 μg/kg IP) shifted choice behavior, significantly decreasing lever pressing and increasing chow intake. Further experiments showed that the adenosine A2A antagonist MSX-3 and the stimulant methylphenidate attenuated the effort-related impairments produced by IL-6, increasing lever pressing and decreasing chow intake in IL-6 treated rats. The same doses of IL-6 did not alter food intake or preference in parallel free-feeding choice studies, demonstrating that these low doses were not altering preference for the high carbohydrate pellets or generally suppressing appetite. Also, IL-6 did not affect body temperature. Microdialysis studies showed that 8.0 μg/kg IL-6 significantly decreased extracellular dopamine in nucleus accumbens core.

Conclusions

In summary, IL-6 reduces the tendency to work for food, even at low doses that do not produce fever or loss of appetite. Dopaminergic mechanisms may be involved in these effort-related effects. This research has implications for the involvement of cytokines in motivational dysfunctions such as anergia and fatigue.

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References

  • Brydon L, Harrison NA, Walker C, Steptoe A, Critchley HD (2008) Peripheral inflammation is associated with altered substantia nigra activity and psychomotor slowing in humans. Biol Psychiat 63(11):1022–1029

    Article  CAS  PubMed  PubMed Central  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 

  • Brown AS, Gershon S (1993) Dopamine and depression. J Neural Transm Gen Sect 91(2–3):75–109

    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

  • 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  PubMed Central  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

  • 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 116(4):529–537

    Article  CAS  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 (2009) Cytokine, sickness behavior, and depression. Immunol Allergy Clin N Am 29:247–264

    Article  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  PubMed Central  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 

  • Dunlop BW, Nemeroff CB (2007) The role of dopamine in the pathophysiology of depression. Arch Gen Psychiat 64(3):327–337

    Article  CAS  PubMed  Google Scholar 

  • Epstein J, Pan H, Kocsis JH, Yang Y, Butler T, Chusid J, Hochberg H, Murrough J, Strohmayer E, Stern E, Silbersweig DA (2006) Lack of ventral striatal response to positive stimuli in depressed versus normal subjects. Am J Psychiat 163(10):1784–1790

    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 191:579–586

    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 

  • 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  PubMed Central  Google Scholar 

  • Felger JC, Cole SW, Pace TW, Hu F, Woolwine BJ, Doho GH, Raison CL, Miller AH (2012) 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  Google Scholar 

  • Felger JC, Li L, Marvar PJ, Woolwine BJ, Harrison DG, Raison CL, Miller AH (2013) Tyrosine metabolism during interferon-alpha administration: association with fatigue and CSF dopamine concentrations. Brain Behav Immun 31:153–160

    Article  CAS  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 

  • Goldsmith DR, Haroon E, Woolwine BJ, Jung MY, Wommack EC, Harvey PD, Treadway MT, Felger JC, Miller AH (2016) Inflammatory markers are associated with decreased psychomotor speed in patients with major depressive disorder. Brain Behav Immun 56:281–288

    Article  CAS  PubMed  Google Scholar 

  • Hanna A, Sledge G, Mayer ML, Hanna N, Einhorn L, Monahan P, Daggy J, Bhatia S (2006) A phase II study of methylphenidate for the treatment of fatigue. Support Care Cancer 14(3):210–215

    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 

  • 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, 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 69:3308-3318

  • Howren MB, Lamkin DM, Suls J (2009) Associations of depression with C reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med 71:171–186

    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 

  • 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 (1991) Design and analysis: a researcher’s handbook, 3rd edn. Prentice-Hall, Englewood Cliffs, N.J

  • Kitagami T, Yamada K, Miura H, Hashimoto R, Nabeshima T, Ohta T (2003) Mechanism of systemically injected interon-alpha impeding monoamine biosynthesis in rats: role of nitric oxide as a signal crossing the blood-brain barrier. Brain Res 978(1–2):104–114

    Article  CAS  PubMed  Google Scholar 

  • 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 152:67–73

    Article  CAS  PubMed  Google Scholar 

  • Larson SJ, Dunn AJ (2001) Behavioral effects of cytokines. Brain Behav Immun 15(4):371–387

    Article  CAS  PubMed  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 

  • Li HC, Zheng LL, Teng JR, Shen MY (2003) Study on anxiety and depressive disorder of inpatients in general hospital. Zhejiang Da Xue Xue Bao Yi Xue Ban 32(4):342–344

    CAS  PubMed  Google Scholar 

  • Lotrich FE (2009) Major depression during interferon-alpha treatment: vulnerability and prevention. Dialogues Clin Neurosci 11:417–425

    PubMed  PubMed Central  Google Scholar 

  • Maes M, Scharpe S, Meltzer HY, Bosmans E, Suy E, Calabrese J, Cosyns P (1993) Relationships between interleukin-6 activity, acute phase proteins, and function of the hypothalamic-pituitary-adrenal axis in severe depression. Psychiatry Res 49:11–27

    Article  CAS  PubMed  Google Scholar 

  • Maes M, Meltzer HY, Bosmans E, Bergmans R, Vandoolaeghe E, Ranjan R, Desnyder R (1995) Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2 and transferrin receptor in major depression. J Affect Disord 34(4):301–309

    Article  CAS  PubMed  Google Scholar 

  • Maes M, Bosmans E, De Jongh R, Kenis G, Vandoolaeghe E, Neels H (1997) Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment resistant depression. Cytokine 9(11):853–858

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  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 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  PubMed Central  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 

  • 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 204(1):103–112

    Article  CAS  PubMed  PubMed Central  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  PubMed Central  Google Scholar 

  • Nunes EJ, Randall PA, Podurgiel S, Correa M, Salamone JD (2013a) 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 37(9 Pt A):2015–2025

    Article  CAS  PubMed  Google Scholar 

  • Nunes EJ, Randall PA, Hart EE, Freeland C, Yohn SE, Baqi Y, Müller CE, López-Cruz L, Correa M, Salamone JD (2013b) Effort-related motivational effects of the VMAT-2 inhibitor tetrabenazine: implications for animal models of the motivational symptoms of depression. J Neurosci 33:19120–19130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nunes EJ, Randall PA, Estrada A, Epling B, Hart EE, Lee CA, Baqi Y, Müller CE, Correa M, Salamone JD (2014) Effort-related motivational effects of the pro-inflammatory cytokine interleukin 1-beta: studies with the concurrent fixed ratio 5/chow feeding choice task. Psychopharmacology 231:727–773

    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, 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  PubMed Central  Google Scholar 

  • Randall PA, Lee CA, Nunes EJ, Yohn SE, Nowak V, Khan B, Shah P, Pandit S, Vemuri VK, Makriyannis A, Baqi Y, Müller CE, Correa M, Salamone JD (2014) The VMAT-2 inhibitor tetrabenazine affects effort-related decision making in a progressive ratio/chow feeding choice task: reversal with antidepressant drugs. PLoS One 9(6):e99320

  • Randall PA, Lee CA, Podurgiel SJ, Hart E, Yohn SE, Jones M, Rowland M, López-Cruz L, Correa M, Salamone JD (2015) Bupropion increases selection of high effort activity in rats tested on a progressive ratio/chow feeding choice procedure: implications for treatment of effort related motivational symptoms. Int J Neuropsychopharmacol 18(2):1–11

  • Salamone JD, Correa M (2002) Motivational views of reinforcement: implications for understanding the behavioral functions of nucleus accumbens dopamine. Behav Brain Res 137(1–2):3–25

    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  PubMed Central  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 104:515–521

    Article  CAS  PubMed  Google Scholar 

  • Salamone JD, Cousins MS, Bucher S (1994) Anhedonia or anergia? Effects of haloperidol and nucleus accumbens (DA) depletion on instrumental response selection in a T-maze cost/benefit procedure. Behav Brain Res 65(2):221–229

    Article  CAS  PubMed  Google Scholar 

  • Salamone JD, Cousins MS, Maio C, Champion M, Turski T, Kovach J (1996) Different behavioral effects of haloperiodol, clozapine and thioridazine in a concurrent lever pressing and feeding procedure. Psychopharmacology 125(2):105–112

    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 160:371–380

    Article  CAS  PubMed  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 191:461–482

    Article  CAS  PubMed  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  PubMed Central  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  PubMed Central  Google Scholar 

  • Salamone JD, Koychev I, Correa M, McGuire P (2015) Neurobiological basis of motivational deficits in psychopathology. Eur Neuropsychopharmacol 25(8):1225–1238

    Article  CAS  PubMed  Google Scholar 

  • Salamone JD, Correa M, Yohn S, Lopez Cruz L, San Miguel N, Alatorre L (2016a) The pharmacology of effort-related choice behavior: dopamine, depression, and individual differences. Behav Processes 127:3–17

  • Salamone JD, Yohn SE, López-Cruz L, San Miguel N, Correa M (2016b) Activational and effort-related aspects of motivation: neural mechanisms and implications for psychopathology. Brain 139(Pt 5):1325–1347

  • Salamone JD, Pardo M, Yohn SE, López-Cruz L, SanMiguel N, Correa M (2016c) Mesolimbic dopamine and the regulation of motivated behavior. Curr Top Behav Neurosci 27:231–257

  • 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 

  • Schindler R, Felgand JA, Dinarello CA (1990) Recombinant C5a stimulates transcription rather than translation of interleukin-1 (IL-1) and tumor necrosis factor: translational signal provided by lipopolysaccharide or IL-1 itself. Blood 76(8):1631–1638

    CAS  PubMed  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  PubMed Central  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 196(4):565–574

    Article  CAS  PubMed  Google Scholar 

  • Sommer S, Danysz W, Russ H, Valastro B, Flik G, Hauber W (2014) The dopamine reuptake inhibitor MRZ-9547 increases progressive ratio responding in rats. Int J Neuropsychopharmacol 17:2045–2056

    Article  CAS  PubMed  Google Scholar 

  • Stein (2008) Depression, anhedonia, and psychomotor symptoms: the role of dopaminergic neurocircuitry. CNS Spectr 13(7):561–565

    Article  PubMed  Google Scholar 

  • Stotz G, Woggon B, Angst J (1999) Psychostimulants in the therapy of treatment-resistant depression: review of the literature and findings from a retrospective study in 65 depressed patients. Dialogues Clin Neurosci 1(3):165–174

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sukoff Rizzo SJ, Neal SJ, Hughes ZA, Beyna M, Rosenzweig-Lipson S, Moss SJ, Brandon NJ (2012) Evidence for sustained elevation of IL-6 in the CNS as a key contributor of depressive-like phenotypes. Transl Psychiatry 2:e199

    Article  CAS  PubMed  PubMed Central  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 

  • 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 203(3):489–499

    Article  CAS  PubMed  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 

  • Yohn SE, Thompson C, Randall PA, Lee CA, Müller CE, Baqi Y, Muller CE, Correa M, Salamone JD (2015a) The VMAT-2 inhibitor tetrabenazine alters effort-related decision making as measured by the T-maze barrier choice task: reversal with the adenosine A2A antagonist MSX-3 and the catecholamine uptake blocker bupropion. Psychopharmacology 232(7):1313–1323

    Article  CAS  PubMed  Google Scholar 

  • Yohn SE, Santerre JL, Nunes EJ, Kozak R, Podurgiel SJ, Correa M, Salamone JD (2015b) The role of dopamine D1 receptor transmission in effort-related choice behavior: effects of D1 agonists. Pharmacol Biochem Behav 135:217–226

    Article  CAS  PubMed  Google Scholar 

  • Yohn SE, Collins SL, Contreras-Mora HM, Errante EL, Rowland MA, Correa M, Salamone JD (2016a) Not all antidepressants are created equal: differential effects of monoamine uptake inhibitors on effort-related choice behavior. Neuropsychopharmacology 41(3):686–694

    Article  CAS  PubMed  Google Scholar 

  • Yohn SE, Lopez-Cruz L, Hutson PH, Correa M, Salamone JD (2016b) Effects of lisdexamfetamine and s-citalopram, alone and in combination, on effort-related choice behavior in the rat. Psychopharmacology 233(6):949–960

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Many thanks to Thomas Lopardo and Laura Cleary for their help with this research. This work was supported by grants to J. Salamone from the UCONN Research Foundation, to M. Correa from Fundació Bancaixa/ U. Jaume I. (P1.1B2010-43), a UCONN Psychology department grant to A. Haley, and a UCONN SURF grant to Y. Arif.

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Authors and Affiliations

  1. Department of Psychological Sciences, University of Connecticut, Storrs, CT, 06269-1020, USA

    Samantha E. Yohn, Yumna Arif, Allison Haley, Guiseppe Tripodi, Noemi San Miguel, Mercè Correa & John D. Salamone

  2. Universität Bonn, Pharma-Zentrum Bonn, Pharmazeutisches Institut, Pharmazeutische Chemie, Bonn, Germany

    Younis Baqi & Christa E. Müller

  3. Department of Chemistry, Sultan Qaboos University, Muscat, Oman

    Younis Baqi

  4. Àrea de Psicobiologia, Campus de Riu Sec, Universitat Jaume I, 12071, Castelló, Spain

    Noemi San Miguel & Mercè Correa

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Yohn, S.E., Arif, Y., Haley, A. et al. Effort-related motivational effects of the pro-inflammatory cytokine interleukin-6: pharmacological and neurochemical characterization. Psychopharmacology 233, 3575–3586 (2016). https://doi.org/10.1007/s00213-016-4392-9

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