Dopamine, Effort-Based Choice, and Behavioral Economics: Basic and Translational Research

Abstract

Operant behavior is not only regulated by factors related to the quality or quantity of reinforcement, but also by the work requirements inherent in performing instrumental actions. Moreover, organisms often make effort-related decisions involving economic choices such as cost/benefit analyses. Effort-based decision making is studied using behavioral procedures that offer choices between high-effort options leading to relatively preferred reinforcers vs. low effort/low reward choices. Several neural systems, including the mesolimbic dopamine (DA) system and other brain circuits, are involved in regulating effort-related aspects of motivation. Considerable evidence indicates that mesolimbic DA transmission exerts a bi-directional control over exertion of effort on instrumental behavior tasks. Interference with DA transmission produces a low-effort bias in animals tested on effort-based choice tasks, while increasing DA transmission with drugs such as DA transport blockers tends to enhance selection of high-effort options. The results from these pharmacology studies are corroborated by the findings from recent articles using optogenetic, chemogenetic and physiological techniques. In addition to providing important information about the neural regulation of motivated behavior, effort-based choice tasks are useful for developing animal models of some of the motivational symptoms that are seen in people with various psychiatric and neurological disorders (e.g., depression, schizophrenia, Parkinson's disease). Studies of effort-based decision making may ultimately contribute to the development of novel drug treatments for motivational dysfunction.

Keywords: accumbens; depression; effort-related decision making; models; motivation; reward; ventral striatum.

Figure 1

Effects of the availability of a food substitute on PROG lever pressing output reinforced by high-carbohydrate pellets. As described in the text, the PROG/chow feeding choice task is one of the behavioral procedures that is used to assess effort-based choice in rodents (Randall et al., , ; Yohn et al., 2016c). This figure presents baseline training data from male Long Evans rats (n = 8) over the last 2 weeks of PROG alone training (Weeks -2 and -1) followed by the first 2 weeks of PROG/chow feeding choice training. As rats transition from the PROG alone schedule to the PROG/chow feeding choice task, in which an alternative food source (laboratory chow) is concurrently available in the chamber, it can be seen that the presence of the available chow significantly suppresses lever pressing output (F_(3,21) = 17.018, p < 0.001). The available chow is acting like a low-cost substitute that shifts demand away from the high-cost Bio-serv pellets that can only be obtained by working on the PROG schedule.

Figure 2

Schematic drawing summarizing the effects of various pharmacological manipulations on PROG/chow feeding choice performance. Interference with dopamine (DA) transmission by giving DA antagonists or tetrabenazine decreases PROG lever pressing but does not suppress chow intake. In fact, chow intake was significantly increased by the D1 antagonist ecopipam, and also increased in animals treated with haloperidol and tetrabenazine that had high baseline rates of lever pressing (Randall et al., 2012, 2014). In contrast, interfering with the unconditioned reinforcing properties of food by reinforcer devaluation (pre-feeding) or by administration of appetite suppressant drugs (CB1 receptor antagonists/inverse agonists) decreases both PROG lever pressing and chow intake. Finally, blockade of adenosine A_2A receptors or inhibition of DA uptake results in increased levels of PROG lever pressing (Randall et al., ; Yohn et al., 2016c).