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

Abstract

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.

A Novel Weight Lifting Task for Investigating Effort and Persistence in Rats

“…Fixed ratio (FR) and progressive ratio (PROG) response schedules have been used effectively to probe the neurological mechanisms of effort-related costbenefit decision-making (e.g., Floresco et al, 2008;Randall et al, 2014;Hart et al, 2017). The concurrent lever-press/chow choice paradigm in particular has been used to examine effort expenditure in relation to generalized behavioral activation (Salamone et al, 2002;Schweimer and Hauber, 2005;Randall et al, 2012), with subtle pharmacological shifts in behaviors being produced by various compounds [see Salamone et al (2018) for recent review]. While lever pressing is an action that can be carried out alongside tethered optogenetic or electrophysiological experimentation with no risk of injury or hardware damage (e.g., Ma et al, 2014;Robinson et al, 2014;Proulx et al, 2018;Lindenbach et al, 2019), lever pressing -even more so than barrier jumping -is a simple, quickly executed motor action.…”

A comparison of implicit and explicit reward learning in low risk alcohol users versus people who binge drink and people with alcohol dependence

“…It is also possible that some of the patients received a medical cessation treatment after the acute withdrawal (e.g., naltrexone, disulfiram, or acamprosate; Tretter, 2017 ). Performance of the patient group in explicit reward learning may have been affected by a possible medication with one of the three medications named above, as they have a high potential to improve conditioned learning and decision making ( Salamone et al, 2018 ). Any medication effects would therefore counteract our hypothesis.…”

Affective biases and their interaction with other reward-related deficits in rodent models of psychiatric disorders

“…As mentioned previously, motivation and effort have become increasingly recognised as a process requiring an intact dopaminergic system (see [198][199][200] for detailed reviews).…”