The behavioral pharmacology of effort-related choice behavior: dopamine, adenosine and beyond

Abstract

For many years, it has been suggested that drugs that interfere with dopamine (DA) transmission alter the "rewarding" impact of primary reinforcers such as food. Research and theory related to the functions of mesolimbic DA are undergoing a substantial conceptual restructuring, with the traditional emphasis on hedonia and primary reward yielding to other concepts and lines of inquiry. The present review is focused upon the involvement of nucleus accumbens DA in effort-related choice behavior. Viewed from the framework of behavioral economics, the effects of accumbens DA depletions and antagonism on food-reinforced behavior are highly dependent upon the work requirements of the instrumental task, and DA-depleted rats show a heightened sensitivity to response costs, especially ratio requirements. Moreover, interference with accumbens DA transmission exerts a powerful influence over effort-related choice behavior. Rats with accumbens DA depletions or antagonism reallocate their instrumental behavior away from food-reinforced tasks that have high response requirements, and show increased selection of low reinforcement/low cost options. Nucleus accumbens DA and adenosine interact in the regulation of effort-related functions, and other brain structures (anterior cingulate cortex, amygdala, ventral pallidum) also are involved. Studies of the brain systems regulating effort-based processes may have implications for understanding drug abuse, as well as symptoms such as psychomotor slowing, fatigue or anergia in depression and other neurological disorders.

Keywords: adenosine; behavioral economics; dopamine; effort; reinforcement; review; work.

Fig 1

This figure is re-drawn based upon data from Salamone (1986). Rats were tested in a large activity chamber, and were reinforced with 45 mg food pellets on a FI-30 sec schedule for being on the floor panel in front of the food dish. Locomotor activity also was recorded, and this procedure allowed for measurement of both the reinforced response of being on the panel (mean ± SEM time on the panel), and schedule-induced activity (mean ± SEM number of activity counts across the 30 min session, divided into five 6-min periods). The effects of 0.4 mg/kg haloperidol were compared with vehicle injections, and with extinction. Figure 1A shows that haloperidol suppressed schedule-induced motor activity. Figure 1B demonstrates that extinction lowered the instrumental response of being on the panel, but haloperidol did not.

Fig 2

This figure shows the effect of ratio requirement on the number of lever presses emitted and operant pellets consumed in rats with accumbens DA depletions compared to rats in the vehicle control group (based upon data from Aberman & Salamone, 1999). The data are represented as a demand curve, calculated from the mean number of reinforcement pellets consumed (presented on a log scale) as a function of ratio requirement. Although comparable levels of consumption in DA depleted and control groups were seen with the FR1 schedule, DA-depleted rats showed markedly reduced consumption relative to the control group at higher ratio levels.

Fig 3

Scatterplot showing relation between baseline or control rates of responding on various interval and ratio schedules of reinforcement versus the magnitude of the suppression of response rate produced by accumbens DA depletions (expressed as mean percent of control responding) in rats responding on that schedule. Solid black circles and regression line are from Salamone et al., (1999). Additional data points are added for the tandem VI30s/FR1 and VI30s/FR5 schedules from Correa et al. (2002; grey triangles), and the tandem VI60s/FR1, VI60s FR10, VI120s/FR1, and VI120s FR10 schedules used by Mingote et al. (2005; open circles).