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
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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.
KeywordsMotivation Dopamine Schizophrenia Bussey-Saksida chambers Panel pressing Preference test
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.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 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 233:393–404PubMedGoogle Scholar
- Keppel G (1991) Design and analysis a researcher’s handbook, 3rd edn. Prentice Hall, Englewood Clifts, NYGoogle Scholar
- 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 138:349–359PubMedGoogle Scholar
- 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):19120–19130PubMedPubMedCentralGoogle Scholar
- 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 247:217–226PubMedGoogle Scholar
- 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 22:21–27Google Scholar
- 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):e47934PubMedPubMedCentralGoogle Scholar
- 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):e99320PubMedPubMedCentralGoogle Scholar
- 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 2:1–11Google Scholar
- 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 160:371–380PubMedGoogle 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 for understanding anergia and psychomotor slowing in depression. Curr Psychiatr Rev 2:267–280Google Scholar
- 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 127:3–17Google Scholar
- 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):208–229Google Scholar
- 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 69:27–34Google Scholar
- 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, CAGoogle Scholar
- 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 232:1313–1323PubMedGoogle Scholar
- 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 109:270–280PubMedGoogle Scholar