Cell Biology

The Brain’s Natural Reward Pathway

We produce natural opioid molecules in our brain, such as endorphins from the pituitary gland. Once produced, these natural opioids are transferred to the ventral tegmental area of the midbrain. The midbrain is also responsible for the production of dopamine, which is an important neurotransmitter molecule that motivates our behavior. When we engage in certain behaviors and as opioids interact with the ventral tegmental area, dopamine is released and moves to the nucleus accumbens. Dopamine then interacts with the neurons associated with the nucleus accumbens, and initiates a cascade of neural connections that results in our feelings of satisfaction, pain relief, and euphoria. These events are considered a part of our brain’s natural reward pathway. When we take synthetic opioids, they work using the same pathway. Likewise, the more opioids that are taken, the greater the feelings we experience.

OPRM1 Gene

As previously mentioned, the OPRM1 plays a role in an individual’s likelihood of becoming addicted to opioids. The OPRM1 gene produces an opioid receptor protein that interacts with opioid molecules, regardless if they are natural or synthetic opioids. It is important to understand the interaction between opioid receptors and dopamine. Dopamine is produced in the brain by dopaminergic neurons, and these neurons interact with gamma aminobutyric acid (GABA) molecules. This interaction is what causes the suppression of dopamine. Specifically, GABA is produced from GABAergic neurons, and travels from these neurons to the dopaminergic neurons to halt dopamine production and release. Therefore, in order to produce and release dopamine, GABA needs to be inhibited. GABA neurons have opioid receptor proteins, such as OPRM1 receptor, across its cell membrane that when bound to opioids, the receptors send a signal into the GABAergic neurons to temporarily halt GABA production. Thus, this decrease in GABA production and release will cause there to be a decrease in the interaction with dopaminergic neurons, and an increase in dopamine production. 

Since our OPRM1 gene might vary from that of another individual, our opioid receptor proteins will also be different and vary in their ability to bind to opioids. If the opioid receptor is better at binding opioid molecules, you may be more likely to develop an opioid use disorder. With that being said, not all synthetic opioids are the same. Opioid is a class of molecules that includes anything that will interact with opioid receptor proteins produced by the OPRM1 gene. Synthetic opioids include medications like vicodin, oxycodone, morphine, codeine, and many more. These opioids vary in how addictive they are, which mainly depends on how fast acting they are and how readily they will bind to opioid receptor proteins. As someone engages in prolonged synthetic opioid use, they require higher doses of opioids in order for the ventral tegmental area to produce sufficient levels of dopamine to feel normal. Individuals with a severe opioid use disorder that terminate opioid intake will suffer from a very limited production of dopamine and dangerous withdrawal symptoms.