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

Yang, Jen-Hau; Presby, Rose E.; Jarvie, Adam A; Rotolo, Renee A.; Fitch, R. Holly; Correa, Mercè; Salamone, John D.

doi:10.1007/s00213-019-05343-8

Cited by 33 publications

(34 citation statements)

References 60 publications

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“…We found that haloperidol decreased the amount of the high value food earned and consumed and increased the amount of chow consumed. These effects of haloperidol have been seen previously in ERC tasks and implicate our task as assaying similar neurobiological constructs as previously described ERC protocols , Salamone et al 1991, Yang et al 2020. Additionally, we tested the effects of the COMT inhibitor tolcapone and found that it did not significantly modulate ERC performance at any of the doses tested.…”

Section: Discussionsupporting

confidence: 74%

“…In order to validate our ERC protocol, we also tested the effects of haloperidol (0.1 mg/kg) as a positive control. Haloperidol has been shown to decrease responding for the high value option in ERC, including a recent study using a touchscreen-based task (Yang et al 2020). Here, we found that haloperidol decreased the amount of strawberry milk earned (t15 = 2.477, p = 0.0272; Figure 3a), but did not significantly increase the amount of chow consumed (t15 = 1.685, p = 0.1126; Figure 3b).…”

Section: Effects Of Haloperidol On Erc Performancesupporting

confidence: 48%

“…There are several paradigms for assessing effort-based decision-making in humans and animal models, including the human Effort Expenditure for Rewards Task (EEfRT), rodent T-maze with barriers, and rodent operant concurrent choice tasks (Botvinick et al 2009, Enomoto et al 2018, Mott et al 2009, Treadway et al 2012. Recently, rodent touchscreen-based versions of the operant concurrent choice effort-related choice (ERC) tasks have been developed (Heath et al 2015, Yang et al 2020.…”

Section: Introductionmentioning

confidence: 99%

“…The dopaminergic system has long been recognized as a critical regulator of ERC performance from studies that utilized systemic manipulations. The D2 antagonist haloperidol biases behavioral toward the low-effort low value option across multiple versions of ERC tasks (Randall et al 2012, Salamone et al 1991, Yang et al 2020. Similarly, the D1 receptor antagonist ecopipam decreases choice of the high-effort arm of a T-maze and decreases lever pressing in a fixed ratio (FR)/concurrent chow paradigm (Yohn et al 2015a).…”

Section: Introductionmentioning

confidence: 99%

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Effects of catechol-O-methyltransferase inhibition on effort-related choice behavior in male mice

DeBrosse

Wheeler

Barrow

et al. 2020

Preprint

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Effort-related choice (ERC) tasks allow animals to choose between high-value reinforcers that require high effort to obtain or low-value/low-effort reinforcers. Dopaminergic neuromodulation regulates effort-related choice behavior. The enzyme catechol-O-methyltransferase (COMT) metabolizes synaptically-released dopamine. COMT is the predominate regulator of dopamine turnover in regions of the brain with low levels of dopamine transporters, including the prefrontal cortex. Here, we evaluated the effects of the COMT inhibitor tolcapone on ERC performance in a touchscreenbased fixed-ratio/concurrent chow assay in male mice. In this task, mice were given the choice between engaging in a fixed number of instrumental responses to acquire a strawberry milk reward and consuming standard lab chow concurrently available on the chamber floor. We found no significant effects of tolcapone treatment on either strawberry milk earned or chow consumed compared to vehicle treatment. In contrast, we found that haloperidol decreased instrumental responding for strawberry milk and increased chow consumption as seen in previously published studies. These data suggest that COMT inhibition does not significantly affect effort-related decision making in a fixed-ratio/concurrent chow task in male mice.

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Section: Discussionsupporting

confidence: 74%

Section: Effects Of Haloperidol On Erc Performancesupporting

confidence: 48%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of catechol-O-methyltransferase inhibition on effort-related choice behavior in male mice

DeBrosse

Wheeler

Barrow

et al. 2020

Preprint

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“…Animals (n = 8) were trained, and after reaching stable levels, they were food-restricted to 4.0 mg of standard chow the night before the test, in order to increase their appetite for the sucrose pellets. This amount of standard food was selected based on previous studies using food restriction Yang et al, 2020). BL with ad libitum food was used as the control condition.…”

Section: Experiments 2: Manipulations That Change the Relative Value Omentioning

confidence: 99%

Preference for Exercise vs. More Sedentary Reinforcers: Validation of an Animal Model of Tetrabenazine-Induced Anergia

Carratalá-Ros

López-Cruz

Miguel

et al. 2020

Front. Behav. Neurosci.

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Physical activities can have intrinsic motivational or reinforcing properties. The choice to engage in voluntary physical activity is undertaken in relation to the selection of other alternatives, such as sedentary behaviors, drugs, or food intake. The mesolimbic dopamine (DA) system plays a critical role in behavioral activation or exertion of effort, and DA antagonism or depletion induces anergia in effort-based decision-making tasks. However, little is known about the neural mechanisms underlying the decisionmaking processes that establish preferences for sedentary vs. activity-based reinforcers. In the present work with male CD1 mice, we evaluated the effect of tetrabenazine (TBZ), a DA-depleting agent, on a three-choice T-maze task developed to assess preference between reinforcers with different behavioral activation requirements and sensory properties [i.e., a running wheel (RW) vs. sweet pellets or a neutral nonsocial odor]. We also studied the effects of TBZ on the forced swim test (FST), which measures climbing and swimming in a stressful setting, and on anxiety tests [dark-light (DL) box and elevated plus maze (EPM)]. In the three-choice task, TBZ reduced time running in the wheel but increased time spent consuming sucrose, thus indicating reduced activation but relatively intact sucrose reinforcement. The effect of TBZ was not mimicked by motivational manipulations that change the value of the reinforcers, such as making the RW aversive or harder to move, food-restricting the animals, inducing a binge-like eating pattern, or introducing social odors. In the FST, TBZ decreased time climbing (most active behavior) and increased immobility but did not affect anxiety in the DL or EPM. These results indicate that the three-choice T-maze task could be useful for assessing DA modulation of preferences for exercise based on activation and effort requirements, differentiating those effects from changes in preference produced by altering physical requirements, food restriction state, and stress during testing.

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Effects of the dopamine depleting agent tetrabenazine on detailed temporal parameters of effort‐related choice responding

Ren

Carratalá-Ros

Ecevitoglu

et al. 2022

J Exper Analysis Behavior

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The dopamine‐depleting agent tetrabenazine alters effort‐based choice, suppressing food‐reinforced behaviors with high response requirements, while increasing selection of low‐cost options. In the present experiments, rats were tested on a concurrent fixed ratio 5/chow feeding choice task, in which high‐carbohydrate Bio‐serv pellets reinforced lever pressing and lab chow was concurrently available. Detailed timing of lever pressing was monitored with an event recording system, and the temporal characteristics of operant behavior seen after 1.0 mg/kg tetrabenazine or vehicle injections were analyzed. Tetrabenazine shifted choice, decreasing lever pressing but increasing chow intake. There was a small effect on the interresponse‐time distribution within ratios, but marked increases in the total duration of pauses in responding. The postreinforcement‐pause (PRP) distribution was bimodal, but tetrabenazine did not increase the duration of PRPs. Tetrabenazine increased time feeding and duration and number of feeding bouts, but did not affect feeding rate or total time spent lever pressing for pellets and consuming chow. Thus, TBZ appears to predominantly affect the relative allocation of lever pressing versus chow, with little alteration in consummatory motor acts involved in chow intake. Tetrabenazine is used to model motivational symptoms in psychopathology, and these effects in rats could have implications for psychiatric research.

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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

Cited by 33 publications

References 60 publications

Effects of catechol-O-methyltransferase inhibition on effort-related choice behavior in male mice

Effects of catechol-O-methyltransferase inhibition on effort-related choice behavior in male mice

Preference for Exercise vs. More Sedentary Reinforcers: Validation of an Animal Model of Tetrabenazine-Induced Anergia

Effects of the dopamine depleting agent tetrabenazine on detailed temporal parameters of effort‐related choice responding

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