Re: ADHD education of critical importance
You done did it again. Made me think, this case, think deeper.
I have a better understanding of neuron internals. Neurons may have over 1000 dendritic branches and each dendrite branch may receive thousands of synapses. Thus each neuron receives thousands of input signals through neurotransmitters bridging each synaptic clef. If the neurotransmitter binds with the receptor type, it results in a small electrical charge in the membrane of our postsynaptic neuron. Key point: The neuron will not fire an action potential until the sum of all of its synaptic electrical charges (potentials) at any one moment equals or exceeds its threshold.
Our neuron has one output cable, its axon. Its singular axon has many terminals. All axon terminal branches output the same neurotransmitter signal. The principle of "one neuron, one neurotransmitter" does have exceptions in motor and auditory neurons but remains true in our discussion limited to norepinephrine and dopamine transmission. Norepi and dopamine are not processed by the same type neuron.
But they most certainly influence each other.
Norepinephrine has a 3 stage reuptake system.
Uptake1: When the receptors on the postsynaptic side are "satisfied", molecular forces moves the transportors carrying the NA back into the presynaptic neuron.
Uptake2: Norepinephrine is sucked into nearby non-neuronal cells. Dopamine assists Uptake2.
Uptake3 or Vesicular uptake. Norepi transported back via Uptake1 into the presynaptic neuron is transported by VMAT into its containers - vesicles - completing the recycling process. Dopamine aids norepinephrine vesicular uptake.
Because dopamine does not share receptors with norepi does not mean dopamine has no influence on available synaptic norepi. Dopamine is very much involved in the reuptake of norepinephrine. Uptake2 sucks up spent norepi that can not be recyled. Dopamine is part of Uptake2 degradation that is partly responsible for signal termination. On the other hand, dopamine is a component of the vesicular uptake system. If vesicular uptake is inefficient, the vesicles have insufficient norepi available to release into the synapse. More norepi is transported into the synapse because of dopamine's role in vesicular uptake.
Dopamine increases synaptically available norepi using the same mechanism as guanfacine. Guanfacine, as a alpha-2 norepi agonist, should help, not inhibit reuptake. Guanfacine, like dopamine, helps the VMAT transporter. VMAT = Vesicular MonoAmine Transporter. Receptors are the primary norepi neuron to neuron signal flow controllers but only one of many signal senders controlling inter-neural functioning.
It reminds me of what a former U.S. President said. "I did not have sex with that woman." True, if oral sex is not sex. Dopamine and norepinephrine are in bed banging each other sans receptor intercourse. Norepinephrine facillates dopamine production too.
I was able to clear up one of my misconceptions. My understanding that neurons are typed to neurotransmitters appears to be accurate. However, my understanding that, for example, all norepi neurons have the entire set of norepi receptors, is incorrect. I assumed that on each call, the subset of activated norepi receptors acted as path switching logic gates. False. Absolutely false. On the contrary. It appears that the paths from norepi source to norepi destinations are hardwired. Neurons with receptors of type norepi alpha-2A agonists appear to be the path or one of the paths to the area in and around the prefrontal cortex. The neural transmission system is designed to transport norepi to the areas with high demand and conversely not transport norepi to areas with concurrent low demand.
People without ADHD can build greater pathway connectivity by mental exertion. Continually learning and improving their knowledge base and skills loads attention and focus functions. The neural pathways respond by forming more synaptic connections. To quote board member, "Free in Freepor;" "Neurons that fire together, wire together." The increase in synaptic connections is a type of memory. Mental exertion helps improve attention and focus skills. But not when ADHD disables the biological neurotransmission strengthening mechanism. We end up with a grossly underdeveloped neuro transmission system in spite of our best efforts.
I have good reasons to believe that ADHD medications can do more than control. In many cases the medications can fix the disorder if the patient works their brains hard while taking the meds. In that case, the temporary control that the meds offer can become permanent given enough time.
There are circumstances and co-existing disorders and diseases that may make a permanent fix impossible.
I like to see two additional sub topics added to this thread. 1) Why CBT is an important part of ADHD symptom control. 2) The symptoms of medication caused imbalances that can be used to identify the causative med and help find an effective solution.
For example, it seems that anxiety indicates an excessive norepi to serotonin ratio. Alternatively it may indicate an excessive norepi to dopamine. Or perhaps excessive norepi to serotonin and dopamine balance is out of whack.
Many doctors feel the best and only solution is to discontinue the medications. That approach itself has one very serious side-effect. It leaves us without control over our ADHD symptoms. I find it totally unacceptable. We can use a little education on medication solutions that can offset ADHD medication persistant side effects without killing ADHD control.