Now, nicotine is a most interesting drug. Nicotine mimics one of the body's most significant neurotransmitter, acetylcholine. This is the neurotransmitter most often associated with cognition in the cerebral cortex. Acetylcholine is the primary carrier of thought and memory in the brain. It is essential to have appropriate levels of acetylcholine to have new memories or recall old memories.
I cruised the net for sources on acetylcholine and the results were positively amazing as you will see from the following excerpts:
Acetyl-L-Carnitine (ALC) is the acetyl ester of carnitine, the carrier of fatty acids across Mitochondrial membranes. Like carnitine, ALC is naturally produced in the body and found in small amounts in some foods. ...Research in recent years has hoisted ALC from its somewhat mundane role in energy production to nutritional cognitive enhancer and neuroprotective agent extraordinaire. Indeed, taken in its entirety, ALC has become one of the premiere “anti-aging” compounds under scientific investigation, especially in relation to brain and nervous system deterioration.
ALC is found in various concentrations in the brain, and its levels are significantly reduced with aging.(1) In numerous studies in animal models, ALC administration has been shown to have the remarkable ability of improving not only cognitive changes, but also morphological (structural) and neurochemical changes. ...ALC has varied effects on cholinergic activity, including promoting the release(2) and synthesis(3) of acetylcholine. Additionally, ALC promotes high affinity uptake of choline, which declines significantly with age.(4) While these cholinergic effects were first described almost a quarter of a century ago,(5) it now appears that this is only the tip of the ALC iceberg. [Gissen, VRP's Nutritional News, March, 1995]
It turns out that Alzheimer's, a veritable epidemic in our country, is directly related to low levels of acetylcholine. In Alzheimer's disease, the neurons that make acetylcholine degenerate, resulting in memory deficits. In some Alzheimer's patients it can be a 90 per cent reduction! But, does anyone suggest smoking and exercising the brain as a possible cure?
Nope. [...]
Work in the Laboratory of Neurochemistry at the Barrow Neurological Institute principally concerns molecules critically involved in such signaling called nicotinic acetylcholine receptors (nAChR). nAChR act throughout the brain and body as "molecular switches" to connect nerve cell circuits involved in essential functions ranging from vision and memory to the control of heart rate and muscle movement.
Defects in nAChR or their loss cause diseases such as myasthenia gravis and epilepsy and can contribute to Alzheimer’s and Parkinson’s diseases and schizophrenia.
nAChR also happen to be the principal targets of tobacco nicotine. ...nicotine-like medicines show promise in the treatment of diseases such as attention deficit/hyperactivity disorder (ADHD) and Tourette’s syndrome and in alleviation of anxiety, pain, and depression, suggesting involvement of nAChR in those disorders.
...We have shown that numbers and function of diverse nAChR subtypes can be influenced by many biologically active substances, ranging from steroids to local anesthetics, and by agents acting on the extracellular matrix, the cytoskeleton, on second messenger signaling, and at the nucleus. We also have shown that chronic nicotine exposure induces numerical upregulation of many diverse nAChR subtypes via a post-transcriptional process that is dominated by effects on intracellular pools of receptors or their precursors.
Some current studies are testing our hypothesis that chronic nicotine exposure, as occurs with habitual use of tobacco products, disables nAChR and the nerve cell circuits they subserve, thereby contributing to long-lasting changes in brain and body function. [Lukas, 1999]
Now, notice in the above account how tricky they were when they said that nicotine ..." That is jargon for "it increases the number of receptors" as well as the amount of acetylcholine. But, of course, the AMA wouldn't let them get away with any of their work if they weren't adding that they have a hypothesis that "habitual use of tobacco products... disables acetylcholine." Never mind that in the beginning they are proposing it as a therapeutic drug for some of the very problems that have risen to almost epidemic numbers in the present time.
Let's say it again: Research shows, however, that daily infusions of nicotine actually INCREASE the number of acetylcholine receptors by up to 40 %. Some researchers, such as the above, brush this finding off by saying "regardless, their function diminishes." But that is not empirically observed. Most people who smoke find a "set point," and once they have reached it, it does not take more and more and more to satisfy it.
How does nicotine act?
There are two major types (or classes) of acetylcholine receptors in the body, and they are commonly named by the other drugs which bind to them: nicotine and muscarine. Muscarinic acetylcholine receptors (mAChRs) can bind muscarine as well as ACh, and they function to change the metabolism...
Acetylcholine acts on nicotine acetylcholine receptors to open a channel in the cell's membrane. Opening such a channel allows certain types of ions (charged atoms) to flow into or out of the cell. ...When ions flow, there is an electrical current, and the same is true in the nervous system. The flowing of ions, or the passing of current, can cause other things to happen, usually those "things" involve the opening of other types of channels and the passing of information from one neuron to another.
Nicotinic AChRs are found throughout the body, but they are most concentrated in the nervous system (the brain, the spinal cord, and the rest of the nerve cells in the body) and on the muscles of the body (in vertebrates).
We say that nicotine acts like ACh at the receptors to activate them, and both substances are called agonists. The opposite type of drug, something that binds to the receptors and does not allow them to be activated is called an antagonist.
...When a substance comes into the body that can interfere with ACh binding to muscle nAChRs, that chemical can cause death in a relatively short time (because you use muscles to do things like breathe). A class of chemicals in snake and other poisonous venoms, neurotoxins, do exactly that. If you are bitten by a krait or a cobra, for example, and enough venom gets into the blood, there will be enough of their neurotoxin in your body to shut down the diaphragm muscle expands your lungs. Without that muscle functioning, the person ceases to breathe and dies of asphyxiation.
One of the reasons we know so much about these receptors is precisely that--plants and people have used substances [acetylcholine antagonists] which cause paralysis and asphyxiation for a long time. Plants use them to prevent being eaten by herbivores. Animals use similar substances to paralyze their prey. At least one human neuromuscular disease is related to nAChRs, and that is myasthenia gravis...
So, as you can see, nAChRs are important to life. ...All known nicotinic receptors do share some common features. They are composed of 5 protein subunits which assemble like barrel staves around a central pore. ...When the ligand (ACh or nicotine) binds to the receptor, it causes the receptor complex to twist and open the pore in the center. [Pugh]
Now, ... did you notice that it says that
"animals use similar substances [acetylcholine antagonists or ANTI-nicotine] to paralyze their prey? We have to wonder about the oft reported conditions of paralysis associated with "alien interactions" and the almost rabid attack on smoking in our society. [...]
Alcohol is a great pretender and can fool at least four types of receptors.
It blocks the acetylcholine receptors... However, unlike nicotine which also binds to the acetylcholine receptors, alcohol doesn't do anything useful while there. It simply sits there and blocks the ability to think. It also acts like cocaine in that it blocks the dopamine reuptake, flooding the brain with "feeling good." Alcohol stimulates the release of endorphins, thus resembling morphine and heroin to a greatly lessened extent, and it modifies and increases the efficiency of the seretonin receptors.
All that in one brew! Gee, it almost makes you want to go and have a few beers! [...]
It seems that the key to this is the fact that learning, hard thinking and pondering, requires that certain brain chemicals - usually acetylcholine - be squirted out at just the right place and in the right quantities. It is becoming clear that the molecules of memory are blind to the kind of memory - whether it is conscious or unconscious - that is occurring. What determines the quality of different kinds of memories is not the molecules that do the storing but the systems in which those molecules act. If they act in the hippocampus, the memories that get recorded are factual and accessible to our consciousness. If the chemicals are acting in the amygdala, they are emotional and mostly inaccessible to conscious awareness.
Working memory, or awareness, involves the frontal lobes of the brain just above and behind the eyebrows. This is what we use when we want to remember a new phone number just long enough to dial it, or to remember what we went to the kitchen for long enough to get it! It is also the place where many different kinds of information is held simultaneously while we are comparing one thing to another. We can have all kinds of things going on there at once. We can look at something, hold this image in working memory along with the memory of something that we have pulled out of long term memory which we wish to compare it to; sounds, smells, and even the ongoing physiological input from our system as we are considering this: does it make us feel peaceful, happy, sad, afraid? ...
As it happens, the cortical connections to the amygdala are actually far greater in primates than in other animals. It seems that more balanced cortical pathways are the evolutionary trend. It is my opinion that we will develop them or perish. A more harmonious integration of emotion and thinking would allow us to both know our TRUE feelings, and why we have them, and to be able to use them more effectively.
