What does it mean to down-regulate? Why does the brain down-regulate dopamine?

Dr. Michael Lovich

Answered January 26, 2019

Think of receptors as a button on the outside of a cell that a signal molecule touches to initiate a system of messengers within the cell to accomplish various functions.

The human body is a receptor based organism. This means that each time a receptor is activated, a subsequent system or pathway is activated.

There are also positive feedback and negative feedback loops. A negative feedback loop would be where a signal turns on a pathway, and the end products of that pathway would prevent stimulation of that initial signal again. A positive feedback loop would be where a signal turns on a pathway, and the end products of that pathway turn on the signal again. In some pathways, one signal will created multiple products, leading to a “ramping up” effect.

Now the cells in the brain are plastic, this means that repetitive use of a positive feedback loop could be too much, so the body will reduce the number of receptors that can stimulate that overdriven pathway, or “Down Regulation.”

This is also known a “developing a tolerance” to certain medications or supplements.” It is seen often in my practice with people who use Valerian Root or other exogenous compounds as sleep aids to help them get to bed.

Here’s an example, let’s say neuron A, fires into neuron B, who then fires into neuron C. Let’s also say that neuron C is a serotonergic neuron that creates serotonin from tryptophan and turns it into melatonin. If you can use an exogenous product like valerian root to stimulate neuron C directly and “knock you out” to get to bed, then neurons A and B, if they are not being used, will atrophy, and the number of receptors on neuron C that receive signals from neuron B, will down regulate.

Regarding dopamine, that is a complex issue. Let’s talk first about a function of dopamine. It’s commonly known as the reward neurotransmitter.

Dopamine in the brain is used in movement, motivation, and reward, but it works to create EFFICIENCY in those systems. Here’s what the research is saying about how Dopamine works in the body, it is tonically active, which means there is a standard TONE of dopamine flow. Let’s say the body recently performed a movement or thought, and the expectation of what would happen matched what actually happened, then your brain would initiate a reward circuit by increasing dopamine to say, “do it that way more.” If expectation did not match reality, your brain would initiate another reward circuit by decreasing dopamine to say, “do it this way less.”

Here’s an interesting hypothetical example to think about. If a Parkinson’s patient is having slowness and rigidity, a Doctor may increase dopamine to improve that symptom, but now a flood of dopamine messes with that reward motor learning efficiency pathway, not only creating overall MORE movement, decreasing the symptoms, but also more inefficient movements increasing the tremor that is usually associated, because every time a motor program is executed the additional flood of dopamine says “do it this way more,” without the appropriate modularity mechanisms in place to make a smooth controlled movement.

So your answer to why does the brain down regulate dopamine is simply, it does so because the end of another pathway says there were RELATIVELY too many effects of increased dopamine in the body.

In clinical practice I find that chasing quanta of neurotransmitters as the cause ends up with me just shooting the messenger. Gotta look upstream at the circuits and brain structures as they are associated with function.

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