Effects of lisdexamfetamine and s-citalopram, alone and in combination, on effort-related choice behavior in the rat

Yohn, Samantha E.; Cruz, Laura López de la; Hutson, Peter H.; Correa, Mercè; Salamone, John D.

doi:10.1007/s00213-015-4176-7

Cited by 63 publications

(69 citation statements)

References 79 publications

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“…Moreover, chronic IFN-α administration reduced effort-based but not freely available sucrose consumption by the monkeys (Felger et al, 2013c). Similar to the effects of IFN-α, peripheral administration of IL-1β to rodents has been shown to decrease effortful responding for sucrose reward over freely available chow, in the absence of a decrease in preference for freely available sucrose over chow (Nunes et al, 2014); an effect that was reversed by lisdexamfetamine (Yohn et al, 2016). Interestingly, peripheral administration of IL-1β in mice at 24 h has been shown to decrease locomotor (wheel running) activity, which was improved by methylphenidate but not modafinil (Bonsall et al, 2015).…”

Section: Biochemical and Behavioral Studies In Laboratory Animalsmentioning

confidence: 85%

Inflammation Effects on Motivation and Motor Activity: Role of Dopamine

Felger

Treadway

2016

Neuropsychopharmacol

318

237

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Motivational and motor deficits are common in patients with depression and other psychiatric disorders, and are related to symptoms of anhedonia and motor retardation. These deficits in motivation and motor function are associated with alterations in corticostriatal neurocircuitry, which may reflect abnormalities in mesolimbic and mesostriatal dopamine (DA). One pathophysiologic pathway that may drive changes in DAergic corticostriatal circuitry is inflammation. Biomarkers of inflammation such as inflammatory cytokines and acute-phase proteins are reliably elevated in a significant proportion of psychiatric patients. A variety of inflammatory stimuli have been found to preferentially target basal ganglia function to lead to impaired motivation and motor activity. Findings have included inflammation-associated reductions in ventral striatal neural responses to reward anticipation, decreased DA and DA metabolites in cerebrospinal fluid, and decreased availability, and release of striatal DA, all of which correlated with symptoms of reduced motivation and/or motor retardation. Importantly, inflammation-associated symptoms are often difficult to treat, and evidence suggests that inflammation may decrease DA synthesis and availability, thus circumventing the efficacy of standard pharmacotherapies. This review will highlight the impact of administration of inflammatory stimuli on the brain in relation to motivation and motor function. Recent data demonstrating similar relationships between increased inflammation and altered DAergic corticostriatal circuitry and behavior in patients with major depressive disorder will also be presented. Finally, we will discuss the mechanisms by which inflammation affects DA neurotransmission and relevance to novel therapeutic strategies to treat reduced motivation and motor symptoms in patients with high inflammation.

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Section: Biochemical and Behavioral Studies In Laboratory Animalsmentioning

confidence: 85%

Inflammation Effects on Motivation and Motor Activity: Role of Dopamine

Felger

Treadway

2016

Neuropsychopharmacol

318

237

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“…Previous studies have shown that administration of TBZ had no significant effect on free food intake in both mice and rats (Nunes et al, 2013;Pardo et al, 2015;Correa et al, 2018;López-Cruz et al, 2018) and did not induce changes in hedonic taste reactivity to sucrose (Pardo et al, 2015). In rats responding on effort-based choice tasks involving lever pressing, TBZ-induced decreases in lever pressing are actually accompanied by increased intake of the concurrently available chow (Nunes et al, 2013;Yohn et al, 2016b). Taken together, these data are consistent with other studies indicating that the TBZ-induced relative shifts in choice behavior do not appear to be due to changes in primary food motivation (Randall et al, 2012(Randall et al, , 2014Nunes et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Diverse tasks have been used in rodents for evaluating behavioral activation and effort-related decision making, including tasks that give animals the option of vigorously working (lever pressing or climbing a barrier) to obtain access to more highly valued reinforcers vs. approaching and consuming a less preferred reinforcer (Cousins et al, 1994;Salamone and Correa, 2002;Salamone et al, 2016;Mott et al, 2009;Mai et al, 2012;Pardo et al, 2012Pardo et al, , 2015Randall et al, 2012;Sommer et al, 2014;Yohn et al, 2015aYohn et al, , 2016bCorrea et al, 2018;SanMiguel et al, 2019). In these tasks, conditions that alter DA transmission, such as administration of DA antagonists or tetrabenazine (TBZ), can alter behavioral activation and reduce selection of high-effort choices in rats (Nunes et al, 2013;Randall et al, 2014;Hosking et al, 2015;Pardo et al, 2015;Yohn et al, 2015aYohn et al, , 2016aContreras-Mora et al, 2018;Rotolo et al, 2019).…”

Section: Introductionmentioning

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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“…This pattern of responding generates a relatively low 756 baseline rate of PROG lever pressing that can be sensitive to drugs that increase behavioral activation. Several DA transport blockers can increase selection of high-effort PROG lever pressing when administered on their own, including MRZ-9547 (Sommer et al, 2014), bupropion (Randall et al, 2015b;Salamone et al, 2016a), lisdexamfetamine (Yohn et al, 2016e), PRX-14040 (Yohn et al, 2016d), and GBR12909 . These results are consistent with studies reporting that there is enhanced selection of high-effort instrumental actions in mice with knockdown of DA transporters (Cagniard et al, 2006), and in mice that have increased expression of DA D2 receptors in nucleus accumbens induced during adulthood (Trifilieff et al, 2013).…”

Section: Pharmacology Of Effort-relatedmentioning

confidence: 99%

“…Other studies in animals have involved direct administration of the proinflammatory cytokines interleukin (IL)-1b and IL-6. In rats tested on the FR5/chow-feeding choice task, a low-effort bias was induced by administration of IL-1b (Nunes et al, 2014;Yohn et al, 2016e) and IL-6 at doses that did not alter food preference or induce fever. These effort-related effects of cytokine administration were reversed by the adenosine A 2A antagonist MSX-3, and also by the DA transport inhibitors lisdexamfetamine and methylphenidate (Nunes et al, 2014;Yohn et al, 2016a,e).…”

Section: Pharmacology Of Effort-relatedmentioning

confidence: 99%

The Psychopharmacology of Effort-Related Decision Making: Dopamine, Adenosine, and Insights into the Neurochemistry of Motivation

et al. 2018

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Effort-based decision making is studied using tasks that offer choices between high-effort options leading to more highly valued reinforcers versus low-effort/low-reward options. These tasks have been used to study the involvement of neural systems, including mesolimbic dopamine and related circuits, in effort-related aspects of motivation. Moreover, such tasks are useful as animal models of some of the motivational symptoms that are seen in people with depression, schizophrenia, Parkinson's disease, and other disorders. The present review will discuss the pharmacology of effort-related decision making and will focus on the use of these tasks for the development of drug treatments for motivational dysfunction. Research has identified pharmacological conditions that can alter effort-based choice and serve as models for depression-related symptoms (e.g., the vesicular monoamine transport-2 inhibitor tetrabenazine and proinflammatory cytokines). Furthermore, tests of effort-based choice have identified compounds that are particularly useful for stimulating high-effort work output and reversing the deficits induced by tetrabenazine and cytokines. These studies indicate that drugs that act by facilitating dopamine transmission, as well as adenosine A antagonists, are relatively effective at reversing effort-related impairments. Studies of effort-based choice may lead to the identification of drug targets that could be useful for treating motivational treatments that are resistant to commonly used antidepressants such as serotonin transport inhibitors.

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Effects of lisdexamfetamine and s-citalopram, alone and in combination, on effort-related choice behavior in the rat

Abstract: LDX can increase work output in rats responding on effort-based choice tasks, which may have implications for understanding the neurochemistry of motivational symptoms in humans.

Cited by 63 publications

References 79 publications

Inflammation Effects on Motivation and Motor Activity: Role of Dopamine

Inflammation Effects on Motivation and Motor Activity: Role of Dopamine

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

The Psychopharmacology of Effort-Related Decision Making: Dopamine, Adenosine, and Insights into the Neurochemistry of Motivation

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