New insights into brain’s reward system: Effects of blocking key neuroreceptors

A recent study conducted in Austria demonstrated that administering drugs that block opioid and dopamine receptors in the brain leads to reduced neural activity in the medial orbitofrontal cortex and several other regions during the receipt of valued rewards. However, these drugs did not show any observable effects on behavior. The paper was published in Human Brain Mapping.

Rewards are stimuli perceived by the brain as beneficial or desirable, eliciting positive emotional responses. These responses motivate behaviors aimed at obtaining such rewards. Rewards may be tangible, like food and money, or intangible, such as praise and social approval. Each of these rewards activates specific brain pathways involved in the reward system.

These neural pathways heavily rely on dopamine and opioid receptors. Dopamine receptors, proteins on the surfaces of neural cells, are activated by the neurotransmitter dopamine. Similarly, opioid receptors are proteins activated by opioid chemicals produced by the body, such as endorphins, as well as by opioid drugs like morphine and heroin.

Dopamine receptors play a crucial role in the motivational aspect of rewards, driving individuals to seek out rewarding experiences. Opioid receptors, conversely, are more closely associated with the pleasure component of rewards, enhancing the enjoyment derived from these experiences.

The study’s lead author, Claudia Massaccesi, and her colleagues aimed to investigate whether blocking these receptors with drugs would affect behavior and brain functioning. They hypothesized that this intervention would diminish the desire and effort exerted, as well as the associated brain activity, when a participant anticipates a reward.

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The study involved 89 healthy volunteers with an average age of 24 years, more than half of whom were female. Participants were instructed not to eat for 6 hours before arriving at the laboratory.

Upon arrival, participants completed an assessment of their current emotions using the Positive and Negative Affect Scale and filled out a questionnaire regarding physical symptoms of any illnesses they might be experiencing. They were also tested for drugs and pregnancy. Subsequently, each participant received a capsule containing either an opioid blocker (50 mg of naltrexone), a dopamine receptor blocker (400 mg of amisulpride), or a placebo (650 mg of mannitol).

A placebo is a substance designed to be indistinguishable from the actual treatment but contains no active components. Therefore, it should not produce any effects other than psychological ones resulting from the belief that one is undergoing treatment and interacting with researchers. In this study, mannitol, a type of sugar alcohol, was used as the placebo as it does not affect opioid or dopamine receptors and should not produce any effect in such a small quantity.

After ingesting their assigned capsule, participants received a snack and waited for 3 hours. Then, they underwent functional magnetic resonance imaging while engaging in a reward task. The task involved receiving different types of rewards: chocolate milk, a mixture of chocolate and regular milk, and just milk. The social reward component consisted of being caressed on the forearm by a same-gender experimenter.

The reward task required the experimenters to announce the reward, followed by participants rating their desire for it on a visual analog scale and squeezing a hand dynamometer to increase their chance of receiving the desired reward. Afterward, the researchers announced the reward each participant would receive. Participants then received their reward, relaxed for a few seconds, and finally rated their enjoyment of the reward.

The results indicated no effects of the treatment (whether the participants received the opioid and dopamine blockers or the placebo) on the intensity of their desire for the rewards. Although participants expressed stronger desires for more desirable rewards, such as chocolate milk over regular milk and longer caresses, and exerted slightly more effort for nonsocial than for social rewards, these differences were not related to the treatment.

Analysis of the functional magnetic resonance imaging data revealed that the opioid blocker reduced activity in specific regions of the brain, including the right medial orbitofrontal cortex, left medial superior frontal gyrus (encompassing the dorsomedial prefrontal cortex), left superior and middle frontal gyrus (including the dorsolateral prefrontal cortex), and right lateral orbitofrontal cortex, when participants received the most valued types of rewards.

Concurrently, participants who received a dopamine blocker exhibited reduced activity in several brain regions, including the right middle frontal gyrus (premotor cortex), right thalamus (ventral lateral nucleus), left precentral gyrus (primary motor cortex), right caudate, Rolandic operculum, and inferior frontal gyrus.

“We showed that blocking the opioid system reduced liking-related activity in OFC [orbitofrontal cortex region of the brain] during the receipt of primary social and nonsocial stimuli, in line with the common currency schema of reward. The findings represent a significant step toward deepening our understanding of the neurochemical and neuroanatomical foundations of wanting and liking of social and nonsocial rewards,” the  study authors concluded.

The study sheds light on the importance of neural pathways that depend on dopamine and opioids for processing social and nonsocial rewards. However, it also has limitations that need to be taken into account, including the small sample size, which might have obscured minor effects. Additionally, the chosen rewards—drinking chocolate milk or receiving a caress from a same-gender researcher—may not be considered highly valuable. Outcomes could differ in scenarios where participants expect more significant rewards and exert greater effort to obtain them.

The paper, “Effects of dopamine and opioid receptor antagonism on the neural processing of social and nonsocial rewards,” was authored by Claudia Massaccesi, Sebastian Korb, Sebastian Götzendorfer, Emilio Chiappini, Matthaeus Willeit, Johan N. Lundström, Christian Windischberger, Christoph Eisenegger, and Giorgia Silani.