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How Dopamine Signaling Can Turn Motivation “On” or “Off”

D1 and D2 receptors mediate motivation levels during cost-benefit evaluations.

Key points

  • Rewards can inspire motivation. But incentivizing your brain with a reward requires that "earning the prize" is worth your time and effort.
  • Cost-benefit analyses involve assessing a reward's value and deciding if its benefits are worth enduring hardship or delaying gratification.
  • New research pinpoints how two dopamine receptors (D1R and D2R) incentivize motivation based on cost-benefit evaluations.
Dopamine is known as "the reward molecule." This diagram illustrates dopaminergic neurons (i.e., dopamine-producing nerve cells) and dopaminergic pathways.
Source: VectorMine/Shutterstock

Motivation often hinges on the value someone's brain places on the reward or "benefits" received in exchange for the "cost" of investing one's time and energy into a specific goal-directed behavior. For example, imagine that you're offered a new job that would double your salary but requires a stressful commute to a dreary office. Currently, you're happily working remotely from home and make enough money to cover all your expenses. Would you take the job?

Cracking the Motivation Code: What Inspires Us to "Just Do It" or Not Do It?

In an attempt to crack the motivation code, neuroscientists have been conducting animal experiments that look at how the non-human primate brain makes a cost-benefit analysis (CBA) when deciding if the trade-off for receiving a reward is worth enduring some discomfort, working harder, or delaying gratification.

A classic approach-avoidance conflict experiment involves pairing different-sized food rewards with bursts of annoying air in a monkey's face. What's happening in the non-human primate brain when a monkey decides that the blast of air is too annoying—and not worth the aggravation and discomfort—required to "win" or "earn" a tiny food reward? How big and incentivizing does the food reward have to be to change the monkey's mind? Does being in a negative mental state marked by anxiety, depression, or pessimism change how the brain values potential rewards and the brain's willingness to endure discomfort to obtain a prize, no matter its size? Neuroscientists around the globe are actively trying to answer these questions.

Earlier this summer, researchers from Kyoto University and MIT published macaque monkey research (Amemori et al., 2021) that identified a specific cortical brain region in the frontal cortex called the pACC, which is connected to subcortical areas in the striatum and appears to turn motivation off during what they call "pessimistic decision-making" by making potential rewards seem worthless or of little value.

This team of researchers led by Ken-ichi Amemori speculated that dopaminergic pathways were also involved in this decision-making process, but their research didn't focus specifically on dopamine signaling or D1 or D2 receptors.

Another team of researchers from the National Institutes for Quantum and Radiological Science and Technology in Japan, led by Yukiko Hori, recently conducted a study that aims "to quantify and directly compare the roles of dopamine signaling via D1R and D2R in motivation based on the costs and benefits in macaque monkeys." Their findings (Hori et al., 2021) on cost-based motivation reward systems were published on July 1 in the peer-reviewed journal PLoS Biology.

To investigate how dopamine signaling affects motivation, Hori's team developed a dopamine-based experiment in macaque monkeys that blocked the D1-like receptor (D1R) and/or the D2-like receptors (D2R) during cost-benefit evaluations while test subjects were in a PET brain scanner.

Together, D1 and D2 Receptors Give Us the Oomph to "Just Do It"

During a series of experiments conducted by Hori et al., monkeys performed both "reward size" tasks and "work/delay" tasks that allowed the neuroscientists to measure how perceived reward size, required effort, and the immediacy of receiving the reward influenced motivation.

 Image credited to Yukiko Hori from National Institutes for Quantum and Radiological Science and Technology
Positron emission tomography (PET) imaging was used to assess the pharmacological manipulation of dopamine receptors in monkeys. The degree of blockade of either D1R or D2R was associated with a reduction in the positive impact of reward amount and increasing delay discounting while performing a task.
Source: Image credited to Yukiko Hori from National Institutes for Quantum and Radiological Science and Technology

Under these experimental conditions, the neuroscientists gave each monkey the opportunity to perform specific tasks to earn rewards while monitoring the brain to observe what was happening when the monkey decided whether or not a reward was worth the effort and how quickly their brain made this decision.

"We systematically manipulated the D1R and D2R of these monkeys by injecting them with specific receptor-binding molecules that dampened their biological responses to [dopamine] DA signaling," corresponding author Takafumi Minamimoto said in an August 2021 news release.

Interestingly, as their paper's title elucidates, the researchers observed that both "D1- and D2-like receptors differentially mediate the effects of dopaminergic transmission on cost-benefit evaluation and motivation in monkeys."

When making a decision about the perceived benefit vs. cost of investing time and effort to receive a reward, motivational incentivization relies on robust D1R and D2R signaling. The strength of these dopamine signals influenced the tendency to prefer immediate but smaller rewards over larger "prizes" that involve a waiting period (i.e., delay discounting). However, workload discounting appears to be an exclusive function of D2 receptors. As the authors explain in the news release:

"It also became clear that dopamine transmission via D1R and D2R regulates the cost-based motivational process by distinct neurobiological processes for benefits or "reward availability" and costs or "energy expenditure associated with the task." However, workload discounting—the process of discounting the value of the rewards based on the proportion of the effort needed—was exclusively related to D2R manipulation."

In conclusion, Hori summed up the significance of her team's findings: "The complementary roles of two dopamine receptor subtypes that our study revealed, in the computation of the cost-benefit trade-off to guide action, will help us decipher the pathophysiology of psychiatric disorders."

Generalized anxiety disorder and major depressive disorders are often marked by a lack of motivation or unwillingness to experience potential discomfort associated with achieving goal-directed behaviors. Kickstarting someone's motivation and drive to "Go for it!" could create an upward spiral of task-related achievement and feelings of fulfillment.

More human studies are needed to advance our understanding of how dopamine-related motivation systems work in the brain and to identify actionable ways that people from all walks of life can overcome motivational roadblocks.

Image of "Dose-dependent occupancy of D1-like receptors following administration of D1R selective blocker" by Yukiko Hori et al. via EurekAlert


Yukiko Hori, Yuji Nagai, Koki Mimura,Tetsuya Suhara, Makoto Higuchi, Sebastien Bouret, Takafumi Minamimoto. "D1- and D2-like Receptors Differentially Mediate the Effects of Dopaminergic Transmission on Cost–Benefit Evaluation and Motivation in Monkeys." PLos Biology (First published: July 01, 2021) DOI: 10.1371/journal.pbio.3001055

Satoko Amemori, Ann M. Graybiel, Ken-ichi Amemori. "Causal Evidence for Induction of Pessimistic Decision-Making in Primates by the Network of Frontal Cortex and Striosomes." Frontiers in Neuroscience (First published: June 30, 2021) DOI: 10.3389/fnins.2021.649167