(ORDO NEWS) — Scientists have been able to demonstrate the loss of sensitivity of dopamine receptors in response to long-term exposure to dopamine. This study was the first in which such experiments were carried out on human cells.
Researchers at North Carolina State University (USA) have demonstrated that human stem cell-derived neuron-like cells can serve as a model for studying addiction-related changes in the nervous system. The new work sheds light on the influence of dopamine on gene activity in neurons and offers a blueprint for further research in this area.
“It’s extremely difficult to study how addiction changes the human brain at the cellular level: nobody wants to experiment on someone else’s brain,” says Albert Keung, the study’s corresponding author and assistant professor of chemical and biomolecular engineering at the University of North Carolina.
“What we have done shows that it is possible to gain a deep understanding of key cellular responses using neuro-like cells from human stem cells.”
It’s about how the cells in our nervous system respond to drugs that have been linked to substance abuse and addiction. The body releases a neurotransmitter called dopamine, which is associated with feelings of satisfaction and is responsible for the functions of motivation and reward.
When neurons in the brain’s “reward pathway” are exposed to dopamine, the cells turn on a specific set of genes that induce feelings of reward. Thus, this hormone makes a person feel good, makes you want to do something and improves your mood.
Many substances cause the body to produce higher levels of dopamine. The list includes drugs ranging from socially acceptable alcohol and nicotine to illicit opiates and cocaine.
The authors of the new work exposed neuro-like cells derived from human stem cells to different levels of dopamine for different periods of time. As it turned out, when cells were exposed to high levels of the neurotransmitter for a long period of time, the corresponding “reward” genes became significantly less sensitive.
Transferring this model to a person, we can say that if one level of dopamine was required to feel motivated, now a higher level is required. Whether the body is able to produce more of this hormone out of nothing is a rhetorical question. Not surprisingly, addiction forces a person to raise dopamine levels artificially.
The problem is that with regular reuptake of dopamine in larger doses than the body produces, its reserves are simply depleted. It takes a long time to restore dopamine levels in the body.
With the refusal of substances that inhibit dopamine receptors or its reuptake, an addicted person may feel a lack of motivation and a deterioration in mood for months, in extreme cases turning into complete apathy and unwillingness to live, which is associated with a reduced level of dopamine. Hence, there is an almost irresistible desire to return to use.
“Our work is the first experimental study to demonstrate desensitization of genes in human neuron-like cells, especially in response to dopamine,” said Ryan Tam, the study’s first author and graduate student at the University of North Carolina. “We don’t need to think that this happens in human cells: we have shown how it happens in them.”
Many questions remain open. For example, could higher levels of dopamine cause desensitization in a shorter time frame?
Or maybe low levels can cause desensitization on longer time scales? Are there threshold levels or is it some kind of linear relationship? How might the presence of other neurotransmitters or bioactive chemicals affect these responses?
According to Keung, the model on which the study is based can provide answers to all these questions in the future.
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