Neurotransmitters

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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