Effort-based decision-making tasks offer animals choices between preferred reinforcers that require high effort to obtain vs. low effort/low reward options. The neural mechanisms of effort-based choice are widely studied in rats, and evidence indicates that mesolimbic dopamine (DA) and related neural systems play a key role. Fewer studies of effort-based choice have been performed in mice.
The present studies used touchscreen operant procedures (Bussey-Saksida boxes) to assess effort-based choice in mice.
CD1 mice were assessed on a concurrent fixed ratio 1 panel pressing/choice procedure. Mice were allowed to choose between rearing to press an elevated panel on the touchscreen for a preferred food (strawberry milkshake) vs. consuming a concurrently available less preferred alternative (high carbohydrate pellets).
The DA D2 antagonist haloperidol (0.05–0.15 mg/kg IP) produced a dose-related decrease in panel pressing. Intake of food pellets was not reduced by haloperidol, and in fact, there was a significant quadratic trend, indicating a tendency for pellet intake to increase at low/moderate doses. In contrast, reinforcer devaluation by removing food restriction substantially decreased both panel pressing and pellet intake. In free-feeding choice tests, mice strongly preferred milkshake vs. pellets. Haloperidol did not affect food intake or preference.
Haloperidol reduced the tendency to work for food, but this reduction was not due to decreases in primary food motivation or preference. Mouse touchscreen procedures demonstrate effects of haloperidol that are similar but not identical to those shown in rats. These rodent studies may be relevant for understanding motivational dysfunctions in humans.
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Bailey MR, Simpson EH, Balsam PD (2016) Neural substrates underlying effort, time, and risk-based decision making in motivated behavior. Neurobiol Learn Mem 133:233–256
Cagniard B, Balsam P, Brunner D, Zhuang X (2006) Mice with chronically elevated dopamine exhibit enhanced motivation, but not learning, for a food reward. Neuropsychopharmacology 31:1362–1370
Chong TT, Bonnelle V, Manohar S, Veromann KR, Muhammed K, Tofaris GK, Hu M, Husain M (2015) Dopamine enhances willingness to exert effort for reward in Parkinson’s disease. Cortex 69:40–46
Correa M, Pardo M, Bayarri P, López-Cruz L, San Miguel N, Valverde O, Ledent C, Salamone JD (2016) Choosing voluntary exercise over sucrose consumption depends upon dopamine transmission: effects of haloperidol in wild type and adenosine A2AKO mice. Psychopharmacology 233:393–404
Correa M, SanMiguel N, López-Cruz L, Carratalá-Ros C, Olivares-García R, Salamone JD (2018) Caffeine modulates food intake depending on the context that gives access to food: comparison with dopamine depletion. Front Psychiatry 9:411
Culbreth AJ, Moran EK, Barch DM (2018a) Effort-based decision-making in schizophrenia. Curr Opin Behav Sci 22:1–6
Culbreth AJ, Moran EK, Barch DM (2018b) Effort-cost decision-making in psychosis and depression: could a similar behavioral deficit arise from disparate psychological and neural mechanisms? Psychol Med 48(6):889–904
Ellenbroek B, Youn J (2016) Rodent models in neuroscience research: is it a rat race? Dis Model Mech 9(10):1079–1087
Filla I, Bailey MR, Schipani E, Winiger V, Mezias C, Balsam PD, Simpson EH (2018) Striatal dopamine D2 receptors regulate effort but not value-based decision making and alter the dopaminergic encoding of cost. Neuropsychopharmacology 43(11):2180–2189
Floresco SB, Tse MTL, Ghods-Sharifi S (2008a) Dopaminergic and glutamatergic regulation of effort- and delay-based decision making. Neuropsychopharmacology 33:1966–1979
Floresco SB, St Onge JR, Ghods-Sharifi S, Winstanley CA (2008b) Cortico-limbic-striatal circuits subserving different forms of cost-benefit decision making. Cogn Affect Behav Neurosci 8(4):375–389
Ghods-Sharifi S, Floresco SB (2010) Differential effects on effort discounting induced by inactivations of the nucleus accumbens core or shell. Behav Neurosci 124(2):179–191
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(2):130–136
Hart EE, Gerson JO, Zoken Y, Garcia M, Izquierdo A (2017) Anterior cingulate cortex supports effort allocation towards a qualitatively preferred option. Eur J Neurosci 46(1):1682–1688
Hart EE, Gerson JO, Izquierdo A (2018) Persistent effect of withdrawal from intravenous methamphetamine self-administration on brain activation and behavioral economic indices involving an effort cost. Neuropharmacology 140:130–138
Heath CJ, Bussey TJ, Saksida LM (2015) Motivational assessment of mice using the touchscreen operant testing system: effects of dopaminergic drugs. Psychopharmacology 232:4043–4057
Hogenkamp PS, Shechter A, St-Onge MP, Sclafani A, Kissileff HR (2017) A sipometer for measuring motivation to consume and reward value of foods and beverages in humans: description and proof of principle. Physiol Behav 171:216–227
Hosking JG, Floresco SB, Winstanley CA (2015) Dopamine antagonism decreases willingness to expend physical, but not cognitive, effort: a compariton of two rodent cost/benefit decision making tasks. Neuropsychopharmacology 40(4):1005–1015
Keppel G (1991) Design and analysis a researcher’s handbook, 3rd edn. Prentice Hall, Englewood Clifts, NY
López-Cruz L, SanMiguel N, Carratala-Ros C, Monferrer L, Salamone JD, Correa M (2018) Dopamine depletion shifts behavior from activity based reinforcers to more sedentary ones and adenosine receptor antagonism reverses that shift: relation to ventral striatum DARPP32 phosphorylation patterns. Neuropharmacology 138:349–359
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
Markou A, Salamone JD, Bussey TJ, Mar AC, Brunner D, Cilmour G, Balsam P (2013) Measuring reinforcement learning and motivation constructs in experimental animals: relevance to the negative symptoms of schizophrenia. Neurosci Biobehav Rev 37(9):2149–2165
Mingote S, Font L, Farrar AM, Vontell R, Worden LT, Stopper CM, Correa M, Salamone JD (2008) Nucleus accumbens adenosine A2A receptors regulate exertion of effort by acting on the ventral striatopallidal pathway. J Neurosci 28(36):9037–9046
Nunes EJ, Randall PA, Hart EE, Freeland C, Yohn SE, Baqi Y, Muller CE, López-Cruz L, Correa M, Salamone JD (2013) Effort-related motivational effects of the VMAT-2 inhibitor tetrabenazine: implications for animal models of the motivational symptoms of depression. J Neurosci 33(49):19120–19130
Pardo M, Lopez-Cruz L, Valverde O, Ledent C, Baqi Y, Muller 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 62:2068–2077
Pardo M, López-Cruz L, Valverde O, Ledent C, Baqi Y, Müller CE, Salamone JD, Correa M (2013) Effect of subtype-selective adenosine receptor antagonists on basal or haloperidol-regulated striatal function: studies of exploratory locomotion and c-Fos immunoreactivity in outbred and A(2A)R KO mice. Behav Brain Res 247:217–226
Pardo M, Lopez-Cruz L, Miguel NS, Salamone JD, Correa M (2015) Selection of sucrose concentration depends on the effort required to obtain it: studies using tetrabenazine, D1, D2, and D3 receptor antagonists. Psychopharmacology 232:2377–2391
Phillips BU, Lopez-Cruz L, Hailwood J, Heath CJ, Saksida LM, Bussey TJ (2018) Translational approaches to evaluating motivation in laboratory rodents: conventional and touchscreen-based procedures. Curr Opin Behav Sci 22:21–27
Randall PA, Pardo M, Nunes EJ, Lopez-Cruz L, Vemuri VK, Makriyannis A, Baqi Y, Muller 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
Randall PA, Lee CA, Nunes EJ, Yohn SE, Nowak V, Khan B, Shah P, Pandit S, Vemuri VK, Makriyannis A, Baqi Y, Muller 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 CE, Podurgiel SJ, Hart E, Yohn SE, Jones M, Rowland M, Lopez-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 2:1–11
Risbrough V, Ji B, Hauger R, Zhou X (2014) Generation and characterization of humanized mice carrying comt158 met/val alleles. Neuropsychopharmacology 39:1823–1832
Robles CF, Johnson AW (2017) Disruptions in effort-based decision-making and consummatory behavior following antagonism of the dopamine D2 receptor. Behav Brain Res 320:431–439
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
Salamone JD, Correa M (2009) Dopamine/adenosine interactions involved in effort-related aspects of food motivation. Appetite 53(3):422–425
Salamone JD, Correa M (2012) The mysterious motivational functions of mesolimbic dopamine. Neuron 76:470–485
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(4):515–521
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(2):221–229
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(2):105–112
Salamone JD, Arizzi MN, 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, reclopride, and fenfluramine on a concurrent choice task. Psychopharmacology 160:371–380
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 Psychiatr Rev 2:267–280
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 dopamine D2 antagonism. Behav Brain Res 201:216–222
Salamone JD, Koychev I, Correa M, McGuire P (2015) Neurobiological basis of motivational deficits in psychopathology. Eur Neuropsychopharmacol 25:1225–1238
Salamone JD, Correa M, Yohn S, Lopez-Cruz L, Miguel NS, Alatorre L (2016a) The pharmacology of effort-related choice behavior: dopamine, depression, and individual differences. Behav Process 127:3–17
Salamone JD, Yohn SE, Lopez-Cruz L, Miguel NS, Correa M (2016b) Activational and effort-related aspects of motivation: neural mechanisms and implications for psychopathology. BRAIN 139:1325–1347
Salamone JD, Correa M, Yohn SE, Yang JH, Somerville M, Rotolo RA, Presby RE (2017) Behavioral activation, effort-based choice, and elasticity of demand for motivational stimuli: basic and translational neuroscience approaches. Motivation Science 3(3):208–229
Salamone JD, Correa M, Ferrigno S, Yang JH, Rotolo R, Presby R (2018a) The psychopharmacology of effort-related decision making: dopamine, adenosine, and insights into the neurochemistry of motivation. Pharmacol Rev 70:747–762
Salamone JD, Correa M, Yang JH, Rotolo R, Presby R (2018b) Dopamine, effort-based choice, and behavioral economics: basic and translational research. Front Behav Neurosci 12:52
SanMiguel N, Pardo M, Carratala-Ros C, López-Cruz L, Salamone JD, Correa M (2018) Individual differences in the energizing effects of caffeine on effort-based decision-making tests in rats. Pharmacol Biochem Behav 69:27–34
Santillán-Urquiza MA, Herrera-Ruiz M, Zamilpa A, Jiménez-Ferrer E, Román-Ramos R, Tortoriello J (2018) Pharmacological interaction of Galphimia glauca extract and natural galphimines with ketamine and haloperidol on different behavioral tests. Biomed Pharmacother 103:879–888
Sharma AK, Gupta S, Patel RK, Wardhan N (2018) Haloperidol-induced parkinsonism is attenuated by varenicline in mice. J Basic Clin Physiol Pharmacol 29(4):395–401
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
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(12):2045–2056
Todder D, Caliskan S, Baune BT (2009) Longitudinal changes of day-time and night-time gross motor activity in clinical responders and non-responders of major depression. World J Biol Psychiatry 10(4):276–284
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
Trifilieff P, Feng B, Urizar E, Winiger V, Ward RD, Taylor KM, Martinez D, Moore H, Balsam PD, Simpson EH, Javitch JA (2013) Increasing dopamine D2 receptor expression in the adult nucleus accumbens enhances motivation. Mol Psychiatry 18:1025–1033
Ward RD, Simpson EH, Richards VL, Deo G, Taylor K, Glendinning JI, Kandel ER, Balsam PD (2012) Dissociation of hedonic reaction to reward and incentive motivation in an animal model of the negative symptoms of schizophrenia. Neuropsychopharmacology 37(7):1699–1707
Winstanley CA, Floresco SB (2016) Deciphering decision making: variation in animal models of effort- and uncertainty-based choice reveals distinct neural circuitries underlying core cognitive processes. J Neurosci 36(48):12069–12079
Yang JH, Presby RE, Jarvie AA, Rotolo RA, Fitch RH, Correa M, Salamone JD (2018) Pharmacological and genetic studies of effort-related decision making using mouse touchscreen procedures: effects of dopamine antagonism and humanized catechol-o-methyltransferase variants. Society for Neuroscience, San Diego, CA
Yohn SE, Thompson C, Randall PA, Lee CA, Müller CE, Baqi Y, Salamone JD (2015) 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 232:1313–1323
Yohn SE, Lopez-Cruz L, Hutson PH, Correa M, Salamone JD (2016a) Effects of lisdexamfetamine and s-citalopram, alone and in combination, on effort-related choice behavior in the rat. Psychopharmacology 233(6):949–960
Yohn SE, Gogoj A, Haque A, Lopez-Cruz L, Haley A, Huxley P, Baskin P, Correa M, Salamone JD (2016b) Evaluation of the effort-related motivational effects of the novel dopamine uptake inhibitor PRX-14040. Pharmacol Biochem Behav 148:84–91
Yohn SE, Errante EL, Rosenbloom-Snow A, Sommerville M, Rowland MA, Tokarski K, Zafar N, Correa M, Salamone JD (2016c) Blockade of uptake for dopamine, but not norepinephrine or 5-HT, increases selection of high effort instrumental activity: implications for treatment of effort-related motivational symptoms in psychopathology. Neuropharmacology 109:270–280
We wish to thank Suzanne Cayer for her help with this project.
This research was supported by a grant to RHF and JS from The University of Connecticut Tier II program, the University of Connecticut Research Foundation (JS), and to MC from MINECO (PSI2015–68497-R) Spain. JS has received grants from, and done consulting work for, Pfizer, Roche, Shire, Prexa, Chronos, Lundbeck and Acadia.
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Yang, J., Presby, R.E., Jarvie, A.A. et al. Pharmacological studies of effort-related decision making using mouse touchscreen procedures: effects of dopamine antagonism do not resemble reinforcer devaluation by removal of food restriction. Psychopharmacology 237, 33–43 (2020). https://doi.org/10.1007/s00213-019-05343-8
- Bussey-Saksida chambers
- Panel pressing
- Preference test