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Where does nicotine act on the nervous system?

In order to properly answer this question, it’s good to have a brief overview of the nervous system. The nervous system can be subdivided into two broad categories, the central nervous system (CNS) and the peripheral nervous system (PNS). Nicotine receptors are found in both the CNS and PNS.

The CNS includes the brain and the spinal column, both of which are protected by bone; the PNS includes all the nerves that branch out from the CNS and end at the organs of the body. Additionally, the PNS can be further subdivided into the somatic (or voluntary nervous system) and the autonomic (or involuntary nervous system).

We first discuss the PNS and the location of nicotine receptors there. Next, we’ll talk about the CNS, most notably the brain, and what role nicotine receptors play there. Peripheral Nervous System (PNS) Somatic Nervous System.

The somatic nervous system is that part of the PNS that plays a role in the voluntary movement of skeletal muscle (as opposed to the autonomic or involuntary nervous system, which will be discussed later). Electrochemical signals begin at the motor cortex of the CNS, are transmitted down the spinal column, and ultimately through the PNS, terminating at their respective muscles via the neuromuscular junction.

The neuromuscular junction is the point at which the nerves end and their electrochemical communication is converted into a release of the neurotransmitter acetylcholine, which then prompts the muscles to move. This occurs by acetylcholine binding to the nicotinic acetylcholine receptors.

 Autonomic Nervous System

The autonomic nervous system is yet further subdivided into two broad categories: (1) the sympathetic nervous system, responsible for the “fight or flight” response and (2) the parasympathetic nervous system, responsible for the “rest and restoration” response.  illustrates the autonomic nervous system.

 Sympathetic Nervous System

The fight or flight response causes a sudden change in bodily functions as a result of a perceived threat in the environment. It diverts blood away from the digestive organs and skin to the muscles, raises the heart rate and blood pressure, dilates the airways of the lungs, and promotes alertness. In other words, it readies the body to react to the perceived threat so that it can either fight or flee from the threat.

These actions occur with the aid of the hormone epinephrine (also known as adrenalin because it comes from the adrenal glands) and the neurotransmitter norepinephrine inthe sympathetic nervous system. (Finally, the neurotransmitter dopamine is also activated but in a more limited manner.) All of these chemicals are collectively known as catecholamines. Norepinephrine and epinephrine bind to adrenergic receptors (also known as adrenoreceptors after adrenalin).

There are two broad subtypes of adrenoreceptors known as alpha- and beta-adrenergic receptors, and many of the blood pressure medications prescribed today act at these sites by blocking them in order to lower blood pressure.

The sympathetic nervous system is also activated by the neurotransmitter acetylcholine. However acetylcholine’s role is more complicated and indirect in that it stimulates receptors that are located between nerve bundles known as ganglion.

The ganglion are located parallel between thespinal cord and the organs in the illustration, which are junctions between the nerves coming from the CNS (also known as preganglionic) to the PNS, with peripheral nerves going to their respective organs (also known as postganglionic).

As stated earlier, at the end organ sites, instead of acetylcholine, epinephrine and norepinephrine act as the neurotransmitters. The only exceptions to that are the adrenal medulla, which can be considered like a giant ganglion, and the sweat glands, which also respond to acetylcholine.

As a reminder, while not directly part of the sympathetic nervous system, acetylcholine is also the neurotransmitter of the somatic nervous system as mentioned previously. Acetylcholine controls voluntary muscles, causing them to react.

Parasympathetic Nervous System

The rest and restoration response of the parasympathetic nervous system has the opposite effect of the sympathetic nervoussystem’s fight or flight response. This response diverts blood from the muscles to the digestive organs and skin, lowers the heart rate and blood pressure, constricts the airways of the lungs, and promotes sleep.

Unlike the sympathetic nervous system, all of these actions are mediated by only one neurotransmitter, acetylcholine, both at the ganglion and at the terminal endings of the organ systems.

Moving blood from the muscles to the other organs aids in digestion and promotes rest so that the body can rejuvenate and prepare for the next threat. However, the ganglionic acetylcholine receptors differ from the terminal end organ acetylcholine receptors.

 Acetylcholine Receptor Subtypes

There are two broadly different acetylcholine receptors: muscarinic and nicotinic acetylcholine receptors. They are named after the major chemical that stimulates each of them: Acetylcholine stimulates both receptors while muscarine stimulates only muscarinic acetylcholine receptors, and nicotine stimulates nicotinic acetylcholine receptors. Nicotinic acetylcholine receptors are located at multiple sites.

These includethe entire ganglion in the sympathetic and parasympathetic nervous system, the adrenal medulla and the sweat glands, which are also part of the sympathetic nervous system, and finally at the neuromuscular junction of the somatic nervous system. Muscarinic acetylcholine receptors are located at the end organ sites of the parasympathetic nervous system, such as the smooth muscles of the gastrointestinal tract, bladder, heart, and blood vessels.

Each of these two acetylcholine receptors has several subtypes, whose functions vary in response to stimulation from acetylcholine. Each receptor subtype responds to different chemicals as well as to acetylcholine, and either nicotine or muscarine (hence the name nicotinic receptor and muscarinic receptor). These receptors are further classified by subtypes in a very complex manner that allows for further sub-specialization.

For nicotine, there are two broad subtypes: neuronal-type and muscle-type. They are further subdivided by their molecular make-up and their genetic similarities. Some are located only in the brain, some in the autonomic ganglia, and others only at the neuromuscular junction, the point at which the somatic nerves terminate on skeletal muscle. In total, nicotinic receptors contain 4 subfamilies comprising 17 subunits.

This further sub-specialization allows the nicotinic receptor subtypes to differ in their response to various chemicals at muscle tissues and nervous tissues. Many of the historical toxins from plants and animals act on either the muscarinic receptor types, such as atropine from the deadly nightshade, or the nicotinic receptor types, such as curare (found on the skin of frogs and used in poison darts), and alpha-bungarotoxin (found in snake venom), which act at the neuromuscular junction leading to paralysis. Acetylcholine’s role is also multiple in the Central Nervous System CNS.

It principally acts as a neuromodulator, which means that it affects many other neurotransmitter systems to coordinate their activity aswell. It plays a very important role in attention, learning, and memory. Many areas of the brain are involved in learning and memory. Patients with Alzheimer’s disease lose acetylcholine nerves at a faster rate than normal, partly explaining the loss of learning and memory as a symptom of the disease. Any chemical that can pass into the brain and block acetylcholine receptors (known as an anticholinergic) therefore can negatively impact learning and memory.

Many of the new medications for Alzheimer’s disease work by blocking the enzyme responsible for breaking down acetylcholine, known as acetylcholinesterase. These acetylcholinesterase inhibitors cause an increase in the amount of acetylcholine and thus improve learning and memory. Acetylcholine also modulates the experience of pain and pleasure in the centers of the brain, known as the limbic areas.

Clearly, there is a strong link between these centers, our emotional life, and the memory centers because the strongest memories are usually elicited by strong emotions linked to pleasure and pain. Because the limbic area is the area of pleasure, this is predominantly part of the “reward system” of the brain.

Acetylcholine nicotinic receptors act in this area to modulate another neurotransmitter-dopamine-which appears to play an important role in addiction, in addition to its role in attention and alertness. Finally, acetylcholine plays a role in appetite regulation, particularly in areas of the brain such as the hypothalamus, which is one of the principle centers acting to regulate appetite. Nicotinic acetylcholine stimulation suppresses appetite. Many anticholinergic medications have the opposite effect and can stimulate appetite.

Terms:

 Neuromuscular  Junction - The junction of the axon terminal of a motor neuron with the muscle fiber responsible for ultimately causing the muscle to contract.

Acetylcholine - A neurotransmitter found in both the peripheral nervous system (PNS) and the central nervous system (CNS). In the PNS, it is involved in both muscle contraction as well as that part of the involuntary nervous system involved with “rest and restoration.” In the CNS, it is involved with memory function.

Epinephrine  (Also known as the hormone adrenaline.)

Acatecholamine derived from tyrosine, an amino acid, which is produced in the adrenal medulla and released into the bloodstream to activate the “fight or flight” response via the sympathetic nervous system.

Catecholamines - Chemicals used as neurotransmitters and produced from the amino acid tyrosine. They include epinephrine, norepinephrine, and dopamine, all of which are produced in the brain as well as in the adrenal medulla, which is part of the sympathetic nervous system.

Ganglion - A mass of tissue, generally nervous, which provides relay points and intermediary connections between different neurological structures in the body, such as the peripheral and central nervous systems.

Preganglionic - The end of the central nervous system as it is communicating with the autonomic nervous system, which is part of the peripheral nervous system.

Postganglionic - The beginning of the autonomic nervous system, which transmits from the central nervous system to the various organs. Nicotinic receptors are located here.

Adrenal medulla - The central part of the adrenal gland surrounded by the adrenal cortex. It produces adrenalin (also known as epinephrine), norepinephrine, and dopamine.

Muscarinic - Referring to muscarine, a chemical that stimulates acetylcholine receptors, located in the brain and the parasympathetic nervous system.

Alphabungarotoxin - A snake venom that binds irreversibly to nicotinic acetylcholine receptors at the neuromuscular junction, causing paralysis and death.

Neuromodulator - A process in which one neuron uses different neurotransmitters to connect to several neurons, as opposed to direct synaptic transmission where one neuron directly reaches another neuron.

Anticholinergic - A substance that blocks the effects of acetylcholine in the nervous system.

Acetylcholinesterase - An enzyme that breaks down acetylcholine, rendering it inactive. Blocking this enzyme leads to a relative increase in acetylcholine.

Limbic areas - A set of brain structures that includes the hippocampus, amygdala, and anterior thalamic nuclei that support a variety of functions including emotion, behavior, and longterm memory. These structures are closely associated with the olfactory structures.

Dopamine - One of the brain’s major neurotransmitters, dopamine is responsible for attention, alertness, decision making, reward, pleasure, and elevated mood.

Hypothalamus - Located below the thalamus, just above the brain stem, this part of the brain links the nervous system to the endocrine system via the pituitary gland.

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