3. Neurotransmitters| mic 08-13 3 | P a g e
Retrieved and modified from
Structure of a typical chemical synapse
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a
target cell across a synapse.
Neurotransmitters are packaged into synaptic vesicles
clustered beneath the membrane in the axon terminal, on the presynaptic side of a
synapse. They are released into and diffuse across the synaptic cleft, where they bind
to specific receptors in the membrane on the postsynaptic side of the synapse.
Release of neurotransmitters usually follows arrival of an action potential at the
synapse, but may also follow graded electrical potentials. Low level "baseline" release
also occurs without electrical stimulation. Many neurotransmitters are synthesized from
plentiful and simple precursors, such as amino acids, which are readily available from
the diet and which require only a small number of biosynthetic steps to convert.
4. Neurotransmitters| mic 08-13 4 | P a g e
Until the early 20th century, scientists assumed that the majority of synaptic
communication in the brain was electrical. However, through the careful histological
examinations of Ramón y Cajal (1852–1934), a 20 to 40 nm gap between neurons,
known today as the synaptic cleft, was discovered. The presence of such a gap
suggested communication via chemical messengers traversing the synaptic cleft, and in
1921 German pharmacologist Otto Loewi (1873–1961) confirmed that neurons can
communicate by releasing chemicals. Through a series of experiments involving the
vagus nerves of frogs, Loewi was able to manually slow the heart rate of frogs by
controlling the amount of saline solution present around the vagus nerve. Upon
completion of this experiment, Loewi asserted that sympathetic regulation of cardiac
function can be mediated through changes in chemical concentrations. Furthermore,
Otto Loewi is accredited with discovering acetylcholine (ACh)—the first known
Some neurons do, however, communicate via electrical synapses
through the use of gap junctions, which allow specific ions to pass directly from one cell
The chemical identity of neurotransmitters is often difficult to determine experimentally.
For example, it is easy using an electron microscope to recognize vesicles on the
presynaptic side of a synapse, but it may not be easy to determine directly what
chemical is packed into them. The difficulties led to many historical controversies over
whether a given chemical was or was not clearly established as a transmitter. In an
effort to give some structure to the arguments, neurochemists worked out a set of
experimentally tractable rules. According to the prevailing beliefs of the 1960s, a
chemical can be classified as a neurotransmitter if it meets the following conditions:
There are precursors and/or synthesis enzymes located in the presynaptic side
of the synapse.
The chemical is present in the presynaptic element.
It is available in sufficient quantity in the presynaptic neuron to affect the
There are postsynaptic receptors and the chemical is able to bind to them.
A biochemical mechanism for inactivation is present.
Modern advances in pharmacology, genetics, and chemical neuroanatomy have greatly
reduced the importance of these rules. A series of experiments that may have taken
several years in the 1960s can now be done, with much better precision, in a few
months. Thus, it is unusual nowadays for the identification of a chemical as a
neurotransmitter to remain controversial for very long periods of time.
5. Neurotransmitters| mic 08-13 5 | P a g e
Types of neurotransmitters
There are many different ways to classify neurotransmitters. Dividing them into amino
acids, peptides, and monoamines is sufficient for some classification purposes.
Amino acids: glutamate,
aspartate, D-serine, γ-aminobutyric acid (GABA),
Monoamines and other biogenic amines: dopamine (DA), norepinephrine
(noradrenaline; NE, NA), epinephrine (adrenaline), histamine, serotonin (SE, 5-
Peptides: somatostatin, substance P, opioid peptides
Others: acetylcholine (ACh), adenosine, anandamide, nitric oxide, etc.
In addition, over 50 neuroactive peptides have been found, and new ones are
discovered regularly. Many of these are "co-released" along with a small-molecule
transmitter, but in some cases a peptide is the primary transmitter at a synapse. β-
endorphin is a relatively well known example of a peptide neurotransmitter; it engages
in highly specific interactions with opioid receptors in the central nervous system.
Single ions, such as synaptically released zinc, are also considered neurotransmitters
as are some gaseous molecules such as nitric oxide (NO), hydrogen sulfide
(H2S), and carbon monoxide (CO).
Because they are not packaged into vesicles they
are not classical neurotransmitters by the strictest definition, however they have all been
shown experimentally to be released by presynaptic terminals in an activity-dependent
By far the most prevalent transmitter is glutamate, which is excitatory at well over 90%
of the synapses in the human brain.
The next most prevalent is GABA, which is
inhibitory at more than 90% of the synapses that do not use glutamate. Even though
other transmitters are used in far fewer synapses, they may be very important
functionally—the great majority of psychoactive drugs exert their effects by altering the
actions of some neurotransmitter systems, often acting through transmitters other than
glutamate or GABA. Addictive drugs such as cocaine and amphetamine exert their
effects primarily on the dopamine system. The addictive opiate drugs exert their effects
primarily as functional analogs of opioid peptides, which, in turn, regulate dopamine
6. Neurotransmitters| mic 08-13 6 | P a g e
Excitatory and inhibitory
Some neurotransmitters are commonly described as "excitatory" or "inhibitory". The only
direct effect of a neurotransmitter is to activate one or more types of receptors. The
effect on the postsynaptic cell depends, therefore, entirely on the properties of those
receptors. It happens that for some neurotransmitters (for example, glutamate), the
most important receptors all have excitatory effects: that is, they increase the probability
that the target cell will fire an action potential. For other neurotransmitters, such as
GABA, the most important receptors all have inhibitory effects (although there is
evidence that GABA is excitatory during early brain development). There are, however,
other neurotransmitters, such as acetylcholine, for which both excitatory and inhibitory
receptors exist; and there are some types of receptors that activate complex metabolic
pathways in the postsynaptic cell to produce effects that cannot appropriately be called
either excitatory or inhibitory. Thus, it is an oversimplification to call a neurotransmitter
excitatory or inhibitory—nevertheless it is convenient to call glutamate excitatory and
GABA inhibitory so this usage is seen frequently.
Main article: Neuromodulation
As explained above, the only direct action of a neurotransmitter is to activate a receptor.
Therefore, the effects of a neurotransmitter system depend on the connections of the
neurons that use the transmitter, and the chemical properties of the receptors that the
transmitter binds to.
Here are a few examples of important neurotransmitter actions:
Glutamate is used at the great majority of fast excitatory synapses in the brain
and spinal cord. It is also used at most synapses that are "modifiable", i.e.
capable of increasing or decreasing in strength. Excess glutamate can
overstimulate the brain and causes seizures.[
Modifiable synapses are thought to
be the main memory-storage elements in the brain. Excessive glutamate release
can lead to excitotoxicity causing cell death.
GABA is used at the great majority of fast inhibitory synapses in virtually every
part of the brain. Many sedative/tranquilizing drugs act by enhancing the effects
of GABA. Correspondingly glycine is the inhibitory transmitter in the spinal cord.
Acetylcholine is distinguished as the transmitter at the neuromuscular junction
connecting motor nerves to muscles. The paralytic arrow-poison curare acts by
blocking transmission at these synapses. Acetylcholine also operates in many
regions of the brain, but using different types of receptors, including nicotinic and
Dopamine has a number of important functions in the brain; this includes
regulation of motor behavior, pleasures related to motivation and also emotional
arousal. It plays a critical role in the reward system; people with Parkinson's
7. Neurotransmitters| mic 08-13 7 | P a g e
disease have been linked to low levels of dopamine and people with
schizophrenia have been linked to high levels of dopamine.
Serotonin is a monoamine neurotransmitter. Most is produced by and found in
the intestine (approximately 90%), and the remainder in central nervous system
neurons. It functions to regulate appetite, sleep, memory and learning,
temperature, mood, behaviour, muscle contraction, and function of the
cardiovascular system and endocrine system. It is speculated to have a role in
depression, as some depressed patients are seen to have lower concentrations
of metabolites of serotonin in their cerebrospinal fluid and brain tissue.
Substance P is an undecapeptide responsible for transmission of pain from
certain sensory neurons to the central nervous system. It also aids in controlling
relaxation of the vasculature and lowering blood pressure through the release of
Opioid peptides are neurotransmitters that act within pain pathways and the
emotional centers of the brain; some of them are analgesics and elicit pleasure
Neurons expressing certain types of neurotransmitters sometimes form distinct
systems, where activation of the system affects large volumes of the brain, called
volume transmission. Major neurotransmitter systems include the noradrenaline
(norepinephrine) system, the dopamine system, the serotonin system and the
Drugs targeting the neurotransmitter of such systems affect the whole system; this fact
explains the complexity of action of some drugs. Cocaine, for example, blocks the
reuptake of dopamine back into the presynaptic neuron, leaving the neurotransmitter
molecules in the synaptic gap longer. Since the dopamine remains in the synapse
longer, the neurotransmitter continues to bind to the receptors on the postsynaptic
neuron, eliciting a pleasurable emotional response. Physical addiction to cocaine may
result from prolonged exposure to excess dopamine in the synapses, which leads to the
downregulation of some postsynaptic receptors. After the effects of the drug wear off,
one might feel depressed because of the decreased probability of the neurotransmitter
binding to a receptor. Prozac is a selective serotonin reuptake inhibitor (SSRI), which
blocks re-uptake of serotonin by the presynaptic cell. This increases the amount of
serotonin present at the synapse and allows it to remain there longer, hence
potentiating the effect of naturally released serotonin.
AMPT prevents the conversion
of tyrosine to L-DOPA, the precursor to dopamine; reserpine prevents dopamine
storage within vesicles; and deprenyl inhibits monoamine oxidase (MAO)-B and thus
increases dopamine levels.
Diseases may affect specific neurotransmitter systems. For example, Parkinson's
disease is at least in part related to failure of dopaminergic cells in deep-brain nuclei, for
example the substantia nigra. Levodopa is a precursor of dopamine, and is the most
widely used drug to treat Parkinson's disease.
8. Neurotransmitters| mic 08-13 8 | P a g e
A brief comparison of the major neurotransmitter systems follows:
System Origin 
locus coeruleus arousal
Lateral tegmental field
motor system, reward, cognition, endocrine,
caudal dorsal raphe nucleus Increase (introversion), mood, satiety, body
temperature and sleep, while decreasing
nociception.rostral dorsal raphe nucleus
basal optic nucleus of Meynert
medial septal nucleus
Category Name Abbreviation Metabotropic Ionotropic
Small: Amino acids Aspartate - -
Small: Amino acids
Small: Amino acids
GABA GABAB receptor
Small: Amino acids Glycine Gly - Glycine receptor
Small: Acetylcholine Acetylcholine Ach
Small: Monoamine Norepinephrine NE Adrenergic -
10. Neurotransmitters| mic 08-13 10 | P a g e
Category Name Abbreviation Metabotropic Ionotropic
GRF - -
PP: Somatostatins Somatostatin
SS: Tachykinins Neurokinin A - -
SS: Tachykinins Neurokinin B - -
SS: Tachykinins Substance P - -
PP: Other Bombesin - -
GRP - -
Gas Nitric oxide NO
Gas Carbon monoxide CO -
Heme bound to
Other Anandamide AEA
Other Adenosine triphosphate ATP P2Y12 P2X receptor
Precursors of neurotransmitters
While intake of neurotransmitter precursors does increase neurotransmitter synthesis,
evidence is mixed as to whether neurotransmitter release (firing) is increased. Even with
increased neurotransmitter release, it is unclear whether this will result in a long-term
increase in neurotransmitter signal strength, since the nervous system can adapt to
changes such as increased neurotransmitter synthesis and may therefore maintain
Some neurotransmitters may have a role in depression, and there is
some evidence to suggest that intake of precursors of these neurotransmitters may be
useful in the treatment of mild and moderate depression.
L-DOPA, a precursor of dopamine that crosses the blood–brain barrier, is used in the
treatment of Parkinson's disease.
For depressed patients where low activity of the neurotransmitter norepinephrine is
implicated, there is only little evidence for benefit of neurotransmitter precursor
administration. L-phenylalanine and L-tyrosine are both precursors for dopamine,
norepinephrine, and epinephrine. These conversions require vitamin B6, vitamin C, and
S-adenosylmethionine. A few studies suggest potential antidepressant effects of L-
phenylalanine and L-tyrosine, but there is much room for further research in this area.
11. Neurotransmitters| mic 08-13 11 | P a g e
Administration of L-tryptophan, a precursor for serotonin, is seen to double the
production of serotonin in the brain. It is significantly more effective than a placebo in
the treatment of mild and moderate depression.
This conversion requires vitamin
5-hydroxytryptophan (5-HTP), also a precursor for serotonin, is also more effective
than a placebo.
Degradation and elimination
A neurotransmitter must be broken down once it reaches the post-synaptic cell to
prevent further excitatory or inhibitory signal transduction. For example, acetylcholine
(ACh), an excitatory neurotransmitter, is broken down by acetylcholinesterase (AChE).
Choline is taken up and recycled by the pre-synaptic neuron to synthesize more ACh.
Other neurotransmitters such as dopamine are able to diffuse away from their targeted
synaptic junctions and are eliminated from the body via the kidneys, or destroyed in the
liver. Each neurotransmitter has very specific degradation pathways at regulatory
points, which may be the target of the body's own regulatory system or recreational
1. "Neurotransmitter" at Dorland's Medical Dictionary
2. Elias, L. J, & Saucier, D. M. (2005). Neuropsychology: Clinical and Experimental
Foundations. Boston: Pearson
3. Robert Sapolsky (2005). "Biology and Human Behavior: The Neurological
Origins of Individuality, 2nd edition". The Teaching Company. "see pages 13 &
14 of Guide Book"
4. Saladin, Kenneth S. Anatomy and Physiology: The Unity of Form and Function.
McGraw Hill. 2009 ISBN 0-07-727620-5
5. "Junctions Between Cells". Retrieved 2010-11-22.
7. Kodirov,Sodikdjon A., Shuichi Takizawa, Jamie Joseph, Eric R. Kandel, Gleb P.
Shumyatsky, and Vadim Y. Bolshakov. Synaptically released zinc gates long-
term potentiation in fear conditioning pathways. PNAS, October 10, 2006.
103(41): 15218-23. doi:10.1073/pnas.0607131103
8. Nitric oxide and other gaseous neurotransmitters
10.Schacter, Gilbert and Weger. Psychology.United States of America.2009.Print.
University of Bristol. "Introduction to Serotonin". Retrieved 2009-10-15.
13.Schacter, Gilbert and Weger. Psychology. 2009.Print.
14.Yadav, V. et al; Ryu, Je-Hwang; Suda, Nina; Tanaka, Kenji F.; Gingrich, Jay A.;
Schütz, Günther; Glorieux, Francis H.; Chiang, Cherie Y. et al. (2008). "Lrp5
12. Neurotransmitters| mic 08-13 12 | P a g e
Controls Bone Formation by Inhibiting Serotonin Synthesis in the Duodenum".
Cell 135 (5): 825–837. doi:10.1016/j.cell.2008.09.059. PMC 2614332.
15.Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. pp. 474 for
noradrenaline system, page 476 for dopamine system, page 480 for serotonin
system and page 483 for cholinergic system. ISBN 0-443-07145-4.
16. Meyers, Stephen (2000). "Use of Neurotransmitter Precursors for Treatment of
Depression". Alternative Medicine Review 5 (1): 64–71. PMID 10696120.
17. Van Praag, HM (1981). "Management of depression with serotonin precursors".
Biol Psychiatry 16 (3): 291–310. PMID 6164407.
Molecular Expressions Photo Gallery: The Neurotransmitter Collection
Endogenous Neuroactive Extracellular Signal Transducers
Neurotransmitter at the US National Library of Medicine Medical Subject
neuroscience for kids website
brain explorer website
wikibooks cellular neurobiology
Supplemental: An overview of neurotransmitters for non-biomedical science
13. Neurotransmitters| mic 08-13 13 | P a g e
The Four Major Neurotransmitters
Neurotransmitters are powerful chemicals that regulate numerous physical and
emotional processes such as mental performance, emotional states and pain response.
Virtually all functions in life are controlled by neurotransmitters. They are the brain's
chemical messengers.Interactions between neurotransmitters, hormones, and the brain
chemicals have a profound influence on overall health and well-being. When our
concentration and focus is good, we feel more directed, motivated, and vibrant.
Unfortunately, if neurotransmitter levels are inadequate these energizing and motivating
signals are absent and we feel more stressed, sluggish, and out-of-control.
Proteins, minerals, vitamins,carbohydrates, and fats are the essential nutrients that
make up your body. Proteins are the essential components of muscle tissue, organs,
blood, enzymes, antibodies, and neurotransmitters in the brain. Your brain needs the
proper nutrients everyday in order to manufacture proper levels of the neurotransmitters
that regulate your mood.
Control the appetite center of the brain
Stimulates Corticotropin Releasing Factor, Adrenalcorticotropic Hormone, & Cortisol
Regulate male and female sex hormone
Modulate mood and thought processes
Controls ability to focus, concentrate, and remember things
The Mind Body Connection
The chemistry of our bodies can alter, and be altered by our every thought and feeling.
Our bodies and our minds are truly interconnected, the health of one depends on the
health of the other.
14. Neurotransmitters| mic 08-13 14 | P a g e
There are many biochemical neurotransmitter imbalances that result in mental
health symptoms such as:
*Blood sugar imbalance
*Food and Chemical allergy
*Heavy Metal Toxicity
*Stimulant and drug intoxication
*Under or overactive thyroid
Disrupted communication between the brain and the body can have serious effects to
ones health both physically and mentally. Depression, anxiety and other mood disorders
are thought to be directly related to imbalances with neurotransmitters. The four major
neurotransmitters that regulate mood are Serotonin, Dopamine, GABA and
The Inhibitory System is the brains braking system, it prevents the signal from
continuing. The inhibitory system slows things down. Serotonin and GABA are
examples of inhibitory neurotransmitters.
GABA (Gamma amino butyric acid) GABA is the major inhibitory neurotransmitter in the
central nervous system. It helps the neurons recover after transmission, reduces anxiety
and stress.It regulates norepinephrine, adrenaline, dopamine, and serotonin, it is a
significant mood modulator.
Serotonin imbalance is one of the most common
contributors to mood problems. Some feel it is a virtual
epidemic in the United States. Serotonin is key to our
feelings of happiness and very important for our emotions
because it helps defend against both anxiety and
depression. You may have a shortage of serotonin if you
have a sad depressed mood, anxiety, panic attacks, low
energy, migraines, sleeping problems, obsession or
compulsions, feel tense and irritable, crave sweets, and
have a reduced interest in sex. Additionally, your hormones
and Estrogen levels can affect serotonin levels and this
may explain why some women have pre-menstrual and
menopausal mood problems. Moreover, daily stress can greatly reduce your serotonin
15. Neurotransmitters| mic 08-13 15 | P a g e
The Excitatory Neurotransmitter System can be related to your car's accelerator. It
allows the signal to go. When the excitatory neurotransmitter system is in drive your
system gets all reved up for action. Without a functioning inhibitory system to put on the
brakes, things (like your mood) can get out of control
Epinephrine also known as adrenaline is a neurotransmitter and hormone essential to
metabolism. It regulates attention, mental focus, arousal, and cognition. It also inhibits
insulin excretion and raises the amounts of fatty acids in the blood. Epinephrine is made
from norepinephrine and is released from the adrenal glands. Low levels have been can
result in fatigue, lack of focus, and difficulty losing weight. High levels have been linked
to sleep problems, anxiety and ADHD.
Dopamine is responsible for motivation, interest, and drive. It is associated with positive
stress states such as being in love, exercising, listening to music, and sex . When we
don't have enough of it we don't feel alive, we have difficulty initiating or completing
tasks, poor concentration, no energy, and lack of motivation. Dopamine also is involved
in muscle control and function. Low Dopamine levels can drive us to use drugs (self
medicate), alcohol, smoke cigarettes, gamble, and/or overeat. High dopamine has been
observed in patients with poor GI function, autism, mood swings, psychosis, and
children with attention disorders.
Glutamate is the major excitatory neurotransmitter in the brain. It is required for
learning and memory. Low levels can lead to tiredness and poor brain activity.
Increased levels of glutamate can cause death to the neurons (nerve cells) in the brain.
Dysfunction in glutamate levels are involved in many neurodegenerative diseases such
as Alzheimer's disease, Parkinson's, Huntington's, and Tourette's. High levels also
contribute to Depression, OCD, and Autism.
Histamine is most commonly known for it's role in allergic reactions but it is also
involved in neurotransmission and can affect your emotions and behavior as well.
Histamine helps control the sleep-wake cycle and promotes the release of epinephrine
and norepinephrine. High histamine levels have been linked to obsessive compulsive
tendencies, depression, and headaches.Low histamine levels can contribute to
paranoia, low libido, fatigue, and medication sensitivities.
Norepinephrine also known as noradrenaline is a excitatory neurotransmitter that is
produced by the adrenal medulla or made from dopamine. High levels of norepinephrine
are linked to anxiety, stress, high blood pressure, and hyperactivity. Low levels are
linked to lack of energy, focus, and motivation.
PEA is an excitatory neurotransmitter made from phenylalanine. It is important in focus
and concentration. High levels are observed in individuals experiencing "mind racing",
sleep problems, anxiety, and schizophrenia. Low PEA is associated with difficulty
paying attention or thinking clearly, and in depression.
16. Neurotransmitters| mic 08-13 16 | P a g e
Neurotransmitter levels can now be determined by a simple and convenient urine test
collected at home. Knowing your neurotransmitter levels can help you correct a problem
today or prevent problems from occuring in the future.
For many years, it has been known in medicine that low levels of these
neurotransmitters can cause many diseases and illnesses. A Neurotransmitter
imbalance can cause:
PMS/ Hormone dysfunction
Obsessions and Compulsions
What causes a neurotransmitter imbalance?
Prolonged periods of stress can deplete neurotransmitters levels. Our fast paced, fast
food society greatly contributes to these imbalances.