Introduction
Neurotransmitters are chemicals that
transmit messages from one nerve cell (neuron) to another. The nerve impulse
travels from the first nerve cell through the axon- a single smooth body
arising from the nerve cell- to the axon
terminal and the synaptic knobs. Each synaptic knob communicates with a
dendrite or cell body of another neuron, and the synaptic knobs contain
neurovesicles that store and release neurotransmitters. The synapse lies
between the synaptic knob and the next cell. For the impulse to continue
traveling across the synapse to reach the next cell, the synaptic knobs release
the neurotransmitter into that space, and the next nerve cell is stimulated to
pick up the impulse and continue it.
Definition
Neurotransmitters are chemicals that
convey information, contained within action potentials, across synaptic clefts
to neighboring target cells [Murphy and Deutsch, 1991].
Neurotransmitters are stored in
small vesicles in the axon terminals of neurons. When the action potential, or
electrical impulse, reaches this point, the neurotransmitters are released from
the vesicles. They cross the synaptic cleft, and bind with receptor sites on
the cell body or dendrites of the adjacent neurons to allow the impulse to
continue its course, or to prevent the impulse from continuing.
Neurotransmitters: Nerve Cell
Chemical Functioning
Many new advances in the
understanding and treatment of psychiatric disorders are related to increased
understanding of neurotransmitters. As the depolarization of neuron reaches the
synapse, the stimuli transfer from an intracellular electrical signal to
extracellular chemical signal. Therefore medications that used to treat
psychiatric disorders operate in around the synaptic cleft and have action at
the neurotransmitter level. Once a neurotransmitter has done its job by
transferring a stimulus to an adjacent neuron, the chemical messenger is
removed from the synaptic area by one of three naturally occurring processes:
l. The neurotransmitter leaves the
area through natural diffusion of a substance from an area of high
concentration to one of low concentration.
2.The neurotransmitter can be broken
down by enzymatic degradation.
3.The neurotransmitter can undergo
reuptake and be transported back into storage in the presynaptic neuron.
Many medications used treat
psychiatric disorders involve these three mechanisms. The selective serotonin
reuptake inhibitor (SSRI) class of antidepressants works by influencing the
reuptake mechanism, whereas Monoamine Oxidase Inhibitors affect the degree of
enzyme degradation that occurs in the synaptic cleft.
Mechanism of impulse transmission
A nerve impulse travels through a
nerve in a long, slender cellular structure called an axon, and it eventually
reaches a structure called the presynaptic membrane, which contains
neurotransmitters to be released in a free space called the synaptic cleft. Freely
flowing neurotransmitter molecules are picked up by receptors (structures that
appear on cellular surfaces that pick up molecules that fit into them like a
"lock and key").
Types of neurotransmitters
Many neurotransmitters exist within
the central and peripheral nervous systems, but only a limited number have
implications for psychiatry. Major categories include
·
Cholinergics
·
Monoamines
·
Amino acids
·
Neuropeptides
Cholinergics:
·
Acetylcholine
Acetylcholine was the first chemical to be
identified and proven as a neurotransmitter (Kruk&Pycock, 1983).
Acetylcholine can be found almost everywhere in the brain, but particularly
high concentrations occur in the basal ganglia and motor cortex of the brain.
It is highly significant in the neurotransmission that occurs at the junctions
of nerves and muscles. Acetylcholinesterase is the enzyme that destroys
acetylcholine or inhibits its activity.
Acetylcholine receptors can be
divided into two types: muscuranic and nicotinic. Many drugs, such as
the older neuroleptic antipsychotics, interact with acetylcholine and its
receptor sites to produce anticholinergic
side effects. These occur when muscuranic acetylcholine receptors are
blocked, and the client experiences dry mouth, blurred vision, constipation,
and urinary retention.
Functions of acetylcholine are
manifold and include sleep, arousal, pain perception, the modulation and
coordination of movement, and memory acquisition and retention.
Monoamines:
·
Norepinephrine
Norepinephrine is the
neurotransmitter that produces activity at the sympathetic postsynaptic nerve
terminals in the ANS resulting in the "fight or flight" responses in
the effector organs. Norepinephrine is concentrated in a small area of the
brain known as the locus ceruleus. It has some modulating effect, and
many studies indicate that client
suffering from mood disorders, particularly major depression, may suffer from a deficit of norepinephrine.
Functions of norepinephrine include the regulation of mood, cognition, perception, locomotion,
cardiovascular functioning, and sleep and arousal.
·
Dopamine
Dopamine pathways arise from the
midbrain and hypothalamus and terminate in the frontal cortex, limbic system,
basal ganglia, and thalamus. Dopaminergic pathways include the substantia
nigra, midbrain, and hypothalamus. Dopamine-containing cells in the midbrain
project to the limbic cortex, which is thought to be the part of the
brain that is disturbed in schizophrenia. Dopamine levels are thought to
be excessively elevated
in some clients suffering from schizophrenia, and most of the drugs used to treat schizophrenia act in part
by decreasing dopamine levels or transmission.
Dopamine functions include
regulation of movements and coordination, emotions, voluntary decisionmaking
ability, and because of its influence on the pituitary gland, it inhibits the
release of prolactin.
·
Serotonin:
Serotonin pathways originate from
cell bodies located in the pons and medulla and project to areas including the
hypothalamus, thalamus, limbic system, cerebral cortex, cerebellum, and spinal
cord.
Serotonin may play a role in
maintaining a normal body temperature, sleep and arousal, libido, appetite,
mood, aggression, pain perception, coordination, and the ability to pursue
goal-directed behavior.
·
Histamine:
The role of histamine in mediating
allergic and inflammatory reactions has been well documented. Its role in the
CNS as a neurotransmitter has only recently been confirmed, and the
availability of information is limited.
·
Amino Acids
Inhibitory Amino Acids
·
Gamma-Aminobutryric Acid (GABA):
GABA has a widespread distribution
in the central nervous, with concentrations in the hypothalamus, hippocampus.
cortex, cerebellum, and basal ganglia of the brain.
Alterations in the GABA system have
been implicated in the etiology of anxiety disorders, movement disorders, and various forms
of epilepsy.
·
Glycine:
The highest concentrations of
glycine in the CNS are found in the spinal cord and brain stem. Glycine appears
to be the neurotransmitter of recurrent inhibition of motor neurons within the
spinal cord, and is possibly involved in the regulation of spinal and brain
stem reflexes.
Excitatory Amino Acids
·
Glutamate and Aspartate:
It has largely descending pathways
that interconnect functional regions of the CNS. They are appearing to be primary
excitatory neurotransmitters in the pyramidal cells of the cortex, the
cerebellum, and the primary sensory afferent systems.
Glutamate and Aspartate function in
the rely of sensory information and in the regulation of various motor and
spinal reflexes.
Neuropeptides
Neuropeptides are classified by the
area of the body in which they are located or by their pharmacological or
functional properties. Although their role as neurotransmitters has not been
clearly established.
·
Opioid Peptides:
Opioid Peptides, which include the
endorphins and enkephalins, have been widely studied. They are found in the
various concentrations in the hypothalamus, thalamus, limbic system midbrain
and brainstem.
Enkephalins also found in the
gastrointestinal tract.
Opioid Peptides released in response
to painful stimuli and may be responsible for producing the analgesic effect
following acupuncture.
·
Substance P:
It was the first neuropeptide to
be discovered. Substance P has been found to be highly concentrated in
sensory fibers, and for this reason is thought to play a role in sensory
transmission, and particularly in the regulation of pain.
·
Somatostatin:
Somatostatin (also called growth
hormone-inhibiting hormone) is found in the cerebral cortex, hippocampus,
thalamus, basal ganglia, brainstem, and spinal cord. It stimulates the turnover
and release of dopamine in the basal ganglia and acetylcholine in the brainstem
and hippocampus.
NEUROTRANSMITTERS IN THE CENTRAL
NERVOUS SYSTEM
Neurotransmitter
|
Locomotion/Function
|
Possible implications for Mental Illness
|
|
l .
C
H
O
L
I
N
E
R
G
I
C
S
|
A. Acetylcholine
|
ANS: Sympathetic and parasympathetic presynaptic nerve terminals;
parasympathetic postsynaptic nerve terminals.
CNS: Cerebral cortex, hippoocampus, limbic structure and basal
ganglia.
Functions: Sleep, arousal,pain, perception,movement,memory.
|
Increased levels:
Depression
Decreasedlevels:
Alzheimer's disease,
Huntington's Chorea,
Parkinson's disease.
|
2.
M
O
N
O
A
M
I
N
E
S
|
A.Norepinephrine
|
ANS:
sympatheric postsynaptic nerve terminals.
CNS:Thalamus,
hypothalamus, limbic system,cerebellum,cerebral cortex.
Functions:
mood, cognition,perception, cardiovascular fnctioning, and sleep and arousal
|
Decreased
Levels:
Depression
Incresed
Levels:
Mania, anxiety
states, schizophrenia
|
B.Dopamine
|
Frontal cortex,limbic system, basal ganglia, thalamus, pituitary and
spinal coatd.
|
Decreased Levels:
Depression and Parkinson’s Disease
Increased levels:
Mania and schizophrenia.
|
|
C.Serotonin
|
Hypothalamus,
thalamus, cerebral cortex, cerebellum, spinal cord.
Functions: Sleep and arousal, libido, appetite, mood, aggression, pain, perception, coordination, judgment |
Decreased
levels:
Depession
Increased
levels:
Anxiety States
|
|
D. Histamine
|
Hypothalamus
|
Decreased Level:
Depression
|
|
3.
A
M
I
N
O
A
C
I
D
S
|
A Gamma-amino-butyric
Acid(GABA)
|
Hypothalamus,hippocamus,
cortex, cerebellum, spinal cord, retina
Fnctions:
recurrent inhibition of motor neurons.
|
Decreased
levels:
Huntington’s
Chorea,Anxiety disorders, schizophrenia and various forms of epilepsy
|
B.Glycine
|
Spinal cord and brain stem
Functions:
Recurrent inhibition of motor neurons.
|
Toxic levels: ‘glycine encephalopathy’, decreased levels are correlated
with motor movements.
|
|
C. Glutamate
and
Aspartate
|
Pyramidal cells
of the cortex, cerebellum, and the primary sensory afferent systems,
hippocampus, thalamus, hypothalamus.
Functions:
relay of sensory information and in the regulation of various motor and
spinal reflexes.
|
Increased
levels:
Huntington’s
Chorea, temporal lobe epilepsy,spinal cerebellat degeneration.
|
|
4.
N
E
U
R
O
P
E
P
T
I
D
E
S
|
A.Endorphins
and
Enkephalins
|
Hypothalamus, thalamus, limbic structures,midbrain and brainstem
Enkephalins are also found in the gastrointestinal tract.
Functions: modulation of pain and reduced peristalsis.
(enkepahlins)
|
Modulation of dopamine activity by opioid peptides may indicate some link
to the symptoms of schizophrenia.
|
B.Substance P
|
Hypothalamus,
limbic structures, midbrain,
brainstem, basal ganglia and spinal cord; also found in GIT and salivary
glands.
Function:
Regulation of pain.
|
Decreased
levels:
Huntington's
chorea
|
|
C. Somatostatin
|
Cerebral cortex, thalamus, basal ganglia, spinal cord.
Function: inhibits release of Norepinephrine, stimulates release
of serotonin, dopamine, and ACTH.
|
Decreased levels:
Alzheimer's disease
Increased Levels:
Huntington's chorea.
|
Conclusion:
Different neurotransmitters are
found in different regions of the brain, allowing for highly differentiated
functions of brain tissue. Many neurotransmitters exist within the central and
peripheral nervous systems, but only a limited number have implications for
psychiatry.
References
l. Townsend M.C. Psychiatric/ Mental
Health Nursing. F.A. Davis Company; Philadelphia: 1993.
2. Fortinash.K.M, Worret. P.A.
Psychiatric Mental Health Nursing.4th ed. Mosby Elsevier; Missouri: 2008.
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