The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body.
there are two types of cells
-Neurons-Glial Cells
Neurons
Each neurone consists of a nucleus situated in the cell body, where outgrowths called processes originate from. The main one of these processes is the axon, which is responsible for carrying outgoing messages from the cell. This axon can originate from the CNS and extend all the way to the body's extremities, effectively providing a highway for messages to go to and from the CNS to these body extremities.
Dendrites are smaller secondary processes that grow from the cell body and axon. On the end of these dendrites lie the axon terminals, which 'plug' into a cell where the electrical signal from a nerve cell to the target cell can be made. This 'plug' (the axon terminal) connects into a receptor on the target cell and can transmit information between cells.
Classification of Neurones
Interneurones - Neurones lying entirely within the CNS
Afferent Neurones - Also known as sensory neurones, these are specialised to send impulses towards the CNS away from the peripheral system
Efferent Neurones - Also known as motor Neurones, these nerve cells carry signals from the CNS to the cells in the peripheral system.
Glial cells
Glial cells are non-neuronal cells that provide support and nutrition, maintain homeostasis, form myelin, and participate in signal transmission in the nervous system. In the human brain, it is estimated that the total number of glia roughly equals the number of neurons, although the proportions vary in different brain areas. Among the most important functions of glial cells are to support neurons and hold them in place; to supply nutrients to neurons; to insulate neurons electrically; to destroy pathogens and remove dead neurons.
Nervous system is generally divided on the basis of anatomy and physiology
Central Nervous System
is made up of the
•spinal cord and
•brain
The spinal cord
•conducts sensory information from the peripheral nervous system (both somatic and autonomic) to the brain
•conducts motor information from the brain to our various effectors
◦skeletal muscles
◦cardiac muscle
◦smooth muscle
◦glands
•serves as a minor reflex center
The brain
•receives sensory input from the spinal cord as well as from its own nerves (e.g., olfactory and optic nerves)
•devotes most of its volume (and computational power) to processing its various sensory inputs and initiating appropriate — and coordinated — motor outputs.
White Matter vs. Gray Matter
Both the spinal cord and the brain consist of
•white matter = bundles of axons each coated with a sheath of myelin
•gray matter = masses of the cell bodies and dendrites — each covered with synapses.
In the spinal cord, the white matter is at the surface, the gray matter inside.
In the brain of mammals, this pattern is reversed. However, the brains of "lower" vertebrates like fishes and amphibians have their white matter on the outside of their brain as well as their spinal cord.
The Meninges
Both the spinal cord and brain are covered in three continuous sheets of connective tissue, the meninges. From outside in, these are the
•dura mater — pressed against the bony surface of the interior of the vertebrae and the cranium
•the arachnoid
•the pia mater
The region between the arachnoid and pia mater is filled with cerebrospinal fluid (CSF).
The Extracellular Fluid (ECF) of the Central Nervous System
The cells of the central nervous system are bathed in a fluid that differs from that serving as the ECF of the cells in the rest of the body.
•The fluid that leaves the capillaries in the brain contains far less protein than "normal" because of the blood-brain barrier, a system of tight junctions between the endothelial cells of the capillaries. This barrier creates problems in medicine as it prevents many therapeutic drugs from reaching the brain.
•cerebrospinal fluid (CSF), a secretion of the choroid plexus. CSF flows uninterrupted throughout the central nervous system
◦through the central cerebrospinal canal of the spinal cord and
◦through an interconnected system of four ventricles in the brain.
CSF returns to the blood through veins draining the brain.
31 pairs of spinal nerves arise along the spinal cord. These are "mixed" nerves because each contain both sensory and motor axons. However, within the spinal column,
•all the sensory axons pass into the dorsal root ganglion where their cell bodies are located and then on into the spinal cord itself.
•all the motor axons pass into the ventral roots before uniting with the sensory axons to form the mixed nerves.
The spinal cord carries out two main functions:
•It connects a large part of the peripheral nervous system to the brain. Information (nerve impulses) reaching the spinal cord through sensory neurons are transmitted up into the brain. Signals arising in the motor areas of the brain travel back down the cord and leave in the motor neurons.
•The spinal cord also acts as a minor coordinating center responsible for some simple reflexes like the withdrawal reflex.
The interneurons carrying impulses to and from specific receptors and effectors are grouped together in spinal tracts.
Crossing Over of the Spinal Tracts
Impulses reaching the spinal cord from the left side of the body eventually pass over to tracts running up to the right side of the brain and vice versa. In some cases this crossing over occurs as soon as the impulses enter the cord. In other cases, it does not take place until the tracts enter the brain itself.
The brain of all vertebrates develops from three swellings at the anterior end of the neural canal of the embryo. From front to back these develop into the
•forebrain (also known as the prosencephalon — shown in light color)
•midbrain (mesencephalon — gray)
•hindbrain (rhombencephalon — dark color) The human brain is shown from behind so that the cerebellum can be seen.
The human brain receives nerve impulses from
•the spinal cord and
•12 pairs of cranial nerves
◦Some of the cranial nerves are "mixed", containing both sensory and motor axons
◦Some, e.g., the optic and olfactory nerves (numbers I and II) contain sensory axons only
◦Some, e.g. number III that controls eyeball muscles, contain motor axons only.
The Hindbrain
The main structures of the hindbrain (rhombencephalon) are the
•medulla oblongata
•pons and
•cerebellum
Medulla oblongata
The medulla looks like a swollen tip to the spinal cord. Nerve impulses arising here
•rhythmically stimulate the intercostal muscles and diaphragm — making breathing possible [More]
•regulate heartbeat
•regulate the diameter of arterioles thus adjusting blood flow.
The neurons controlling breathing have mu (µ) receptors, the receptors to which opiates, like heroin, bind. This accounts for the suppressive effect of opiates on breathing. [Discussion] Destruction of the medulla causes instant death.
Pons
The pons seems to serve as a relay station carrying signals from various parts of the cerebral cortex to the cerebellum. Nerve impulses coming from the eyes, ears, and touch receptors are sent on the cerebellum. The pons also participates in the reflexes that regulate breathing.
The reticular formation is a region running through the middle of the hindbrain (and on into the midbrain). It receives sensory input (e.g., sound) from higher in the brain and passes these back up to the thalamus. The reticular formation is involved in sleep, arousal (and vomiting).
Cerebellum
The cerebellum consists of two deeply-convoluted hemispheres. Although it represents only 10% of the weight of the brain, it contains as many neurons as all the rest of the brain combined.
Its most clearly-understood function is to coordinate body movements. People with damage to their cerebellum are able to perceive the world as before and to contract their muscles, but their motions are jerky and uncoordinated.
So the cerebellum appears to be a center for learning motor skills (implicit memory). Laboratory studies have demonstrated both long-term potentiation (LTP) and long-term depression (LTD) in the cerebellum.
The Midbrain
The midbrain (mesencephalon) occupies only a small region in humans (it is relatively much larger in "lower" vertebrates). We shall look at only three features:
•the reticular formation: collects input from higher brain centers and passes it on to motor neurons.
•the substantia nigra: helps "smooth" out body movements; damage to the substantia nigra causes Parkinson's disease.
•the ventral tegmental area (VTA): packed with dopamine-releasing neurons that
◦are activated by nicotinic acetylcholine receptors and
◦whose projections synapse deep within the forebrain.
The VTA seems to be involved in pleasure: nicotine, amphetamines and cocaine bind to and activate its dopamine-releasing neurons and this may account — at least in part (see below)— for their addictive qualities.
The midbrain along with the medulla and pons are often referred to as the "brainstem".
The Forebrain
The human forebrain (prosencephalon) is made up of
•a pair of large cerebral hemispheres, called the telencephalon. Because of crossing over of the spinal tracts, the left hemisphere of the forebrain deals with the right side of the body and vice versa.
•a group of structures located deep within the cerebrum, that make up the diencephalon.
Diencephalon
We shall consider four of its structures: the
•Thalamus.
◦All sensory input (except for olfaction) passes through these paired structures on the way up to the
somatic-sensory regions of the cerebral cortex and then returns to them from there.
◦signals from the cerebellum pass through them on the way to the motor areas of the cerebral cortex.
•Lateral geniculate nucleus (LGN).
All signals entering the brain from each optic nerve enter a LGN and undergo some processing before moving on the various visual areas of the cerebral cortex.
•Hypothalamus.
◦The seat of the autonomic nervous system. Damage to the hypothalamus is quickly fatal as the normal
homeostasis of body temperature, blood chemistry, etc. goes out of control.
◦The source of 8 hormones, two of which pass into the posterior lobe of the pituitary gland.
•Posterior lobe of the pituitary.
Receives
◦vasopressin and
◦oxytocin
from the hypothalamus and releases them into the blood. Link to discussion of the pituitary.
Each hemisphere of the cerebrum is subdivided into four lobes visible from the outside:
•frontal
•parietal
•occipital
•temporal
Hidden beneath these regions of each cerebral cortex is
•a striatum; they receive input from the frontal lobes and also from the limbic system (below). At the base of each striatum is a
•nucleus accumbens (NA).
The pleasurable (and addictive) effects of amphetamines, cocaine, and perhaps other psychoactive drugs seem to depend on their producing increasing levels of dopamine at the synapses in the nucleus accumbens (as well as the VTA).
•a limbic system; they receives input from various association areas in the cerebral cortex and pass signals on to the nucleus accumbens. Each limbic system is made up of a:
◦hippocampus. It is essential for the formation of long-term memories
◦an amygdala
The amygdala appears to be a center of emotions (e.g., fear). It sends signals to the hypothalamus and medulla which can activate the flight or fight response of the autonomic nervous system.
the amygdala contains receptors for
■vasopressin whose activation increases aggressiveness and other signs of the flight or fight response;
■oxytocin whose activation lessens the signs of stress.
The amygdala receives a rich supply of signals from the olfactory system, and this may account for the powerful effect that odor has on emotions (and evoking memories).
Peripheral Nervous System
•sensory neurons running from stimulus receptors that inform the CNS of the stimuli
•motor neurons running from the CNS to the muscles and glands - called effectors - that take action.
The peripheral nervous system is subdivided into the
•sensory-somatic nervous system and the
•autonomic nervous system
The Sensory-Somatic Nervous System
The sensory-somatic system consists of
•12 pairs of cranial nerves and
•31 pairs of spinal nerves.
The Cranial Nerves
Nerves Type Function
IOlfactory sensory olfaction (smell)
IIOptic sensory vision(Contain 38% of all the axons connecting to the brain.)
IIIOculomotor motor* eyelid and eyeball muscles
IVTrochlear motor* eyeball muscles
VTrigeminal mixed Sensory: facial and mouth sensation Motor: chewing
VIAbducens motor* eyeball movement
VIIFacial mixed Sensory: taste Motor: facial muscles and salivary glands
VIIIAuditory sensory hearing and balance
IX Glossopharyngeal mixed Sensory: taste Motor: swallowing
X Vagus mixed main nerve of the parasympathetic nervous system (PNS)
XIAccessory motor swallowing; moving head and shoulder
XII Hypoglossal motor* tongue muscles
*Note: These do contain a few sensory neurons that bring back signals from the muscle spindles in the muscles they control.
The Spinal Nerves
All of the spinal nerves are "mixed"; that is, they contain both sensory and motor neurons.
All our conscious awareness of the external environment and all our motor activity to cope with it operate through the sensory-somatic division of the PNS.
The Autonomic Nervous System
The autonomic nervous system consists of sensory neurons and motor neurons that run between the central nervous system (especially the hypothalamus and medulla oblongata) and various internal organs such as the:
•lungs
•viscera
•glands (both exocrine and endocrine)
It is responsible for monitoring conditions in the internal environment and bringing about appropriate changes in them. The contraction of both smooth muscle and cardiac muscle is controlled by motor neurons of the autonomic system.
The actions of the autonomic nervous system are largely involuntary (in contrast to those of the sensory-somatic system). It also differs from the sensory-somatic system is using two groups of motor neurons to stimulate the effectors instead of one.
•The first, the preganglionic neurons, arise in the CNS and run to a ganglion in the body. Here they synapse with
•postganglionic neurons, which run to the effector organ (cardiac muscle, smooth muscle, or a gland).
The autonomic nervous system has two subdivisions, the
•sympathetic nervous system and the
•parasympathetic nervous system.
The Sympathetic Nervous System
The preganglionic neuron may do one of three things in the sympathetic ganglion:
•synapse with postganglionic neurons (shown in white) which then reenter the spinal nerve and ultimately pass out to the sweat glands and the walls of blood vessels near the surface of the body.
•pass up or down the sympathetic chain and finally synapse with postganglionic neurons in a higher or lower ganglion
•leave the ganglion by way of a cord leading to special ganglia (e.g. the solar plexus) in the viscera. Here it may synapse with postganglionic sympathetic neurons running to the smooth muscular walls of the viscera. However, some of these preganglionic neurons pass right on through this second ganglion and into the adrenal medulla. Here they synapse with the highly-modified postganglionic cells that make up the secretory portion of the adrenal medulla.
The neurotransmitter of the preganglionic sympathetic neurons is acetylcholine (ACh). It stimulates action potentials in the postganglionic neurons.
The neurotransmitter released by the postganglionic neurons is noradrenaline (also called norepinephrine).
The action of noradrenaline on a particular gland or muscle is excitatory is some cases, inhibitory in others. (At excitatory terminals, ATP may be released along with noradrenaline.)
The release of noradrenaline
•stimulates heartbeat
•raises blood pressure
•dilates the pupils
•dilates the trachea and bronchi
•stimulates the conversion of liver glycogen into glucose
•shunts blood away from the skin and viscera to the skeletal muscles, brain, and heart
•inhibits peristalsis in the gastrointestinal (GI) tract
•inhibits contraction of the bladder and rectum
•and, at least in rats and mice, increases the number of AMPA receptors in the hippocampus and thus increases long-term potentiation (LTP).
In short, stimulation of the sympathetic branch of the autonomic nervous system prepares the body for emergencies: for "fight or flight" (and, perhaps, enhances the memory of the event that triggered the response).
Activation of the sympathetic system is quite general because
•a single preganglionic neuron usually synapses with many postganglionic neurons;
•the release of adrenaline from the adrenal medulla into the blood ensures that all the cells of the body will be exposed to sympathetic stimulation even if no postganglionic neurons reach them directly.
The Parasympathetic Nervous System
The main nerves of the parasympathetic system are the tenth cranial nerves, the vagus nerves. They originate in the medulla oblongata. Other preganglionic parasympathetic neurons also extend from the brain as well as from the lower tip of the spinal cord.
Each preganglionic parasympathetic neuron synapses with just a few postganglionic neurons, which are located near — or in — the effector organ, a muscle or gland. Acetylcholine (ACh) is the neurotransmitter at all the pre- and many of the postganglionic neurons of the parasympathetic system. However, some of the postganglionic neurons release nitric oxide (NO) as their neurotransmitter.
Parasympathetic stimulation causes
•slowing down of the heartbeat
•lowering of blood pressure
•constriction of the pupils
•increased blood flow to the skin and viscera
•peristalsis of the GI tract
In short, the parasympathetic system returns the body functions to normal after they have been altered by sympathetic stimulation. In times of danger, the sympathetic system prepares the body for violent activity. The parasympathetic system reverses these changes when the danger is over.
The vagus nerves also help keep inflammation under control. Inflammation stimulates nearby sensory neurons of the vagus. When these nerve impulses reach the medulla oblongata, they are relayed back along motor fibers to the inflamed area. The acetylcholine from the motor neurons suppresses the release of inflammatory cytokines, e.g., tumor necrosis factor (TNF), from macrophages in the inflamed tissue.
Although the autonomic nervous system is considered to be involuntary, this is not entirely true. A certain amount of conscious control can be exerted over it as has long been demonstrated by practitioners of Yoga and Zen Buddhism. During their periods of meditation, these people are clearly able to alter a number of autonomic functions including heart rate and the rate of oxygen consumption. These changes are not simply a reflection of decreased physical activity because they exceed the amount of change occurring during sleep or hypnosis.
Neurotransmission The coordination of cellular activities in animals is usually considered to involve
•an endocrine system: where the response is to hormones: chemicals secreted into the blood by endocrine glands and carried by the blood to the responding cell.
•a nervous system: response to electrical impulses passing from the central nervous system to muscles and glands.
But, in fact, coordination by the nervous system is also chemical. Most neurons achieve their effect by releasing chemicals, the neurotransmitters, on a receiving cell:
•another neuron (a "postsynaptic" neuron)
•a muscle cell
•a gland cell
So the real distinction between nervous and endocrine coordination is that nervous coordination is
•faster and
•more localized
(Neurotransmitters are chemicals that act in a paracrine fashion.)
Synapse
The junction between the axon terminals of a neuron and the receiving cell is called a synapse. (Synapses at muscle fibers are also called neuromuscular junctions or myoneural junctions.)
•Action potentials travel down the axon of the neuron to its end(s), the axon terminal(s).
•Each axon terminal is swollen forming a synaptic knob.
•The synaptic knob is filled with membrane-bounded vesicles containing a neurotransmitter.
•Arrival of an action potential at the synaptic knob opens Ca2+ channels in the plasma membrane.
•The influx of Ca2+ triggers the exocytosis of some of the vesicles.
•Their neurotransmitter is released into the synaptic cleft.
•The neurotransmitter molecules bind to receptors on the postsynaptic membrane.
•These receptors are ligand-gated ion channels.
Excitatory synapses
The neurotransmitter at excitatory synapses depolarizes the postsynaptic membrane (of a neuron in this diagram).
Example: acetylcholine (ACh)
•Binding of acetylcholine to its receptors on the postsynaptic cell opens up ligand-gated sodium channels.
•These allow an influx of Na+ ions, reducing the membrane potential.
•This reduced membrane potential is called an excitatory postsynaptic potential or EPSP.
•If depolarization of the postsynaptic membrane reaches threshold, an action potential is generated in the postsynaptic cell.
Link to further discussion of the electrical events at excitatory synapses.
Inhibitory synapses
The neurotransmitter at inhibitory synapses hyperpolarizes the postsynaptic membrane.
Example: gamma aminobutyric acid (GABA) at certain synapses in the brain.
•The GABAA receptor is a ligand-gated chloride channel. Binding of GABA to the receptors increases the influx of chloride (Cl−) ions into the postsynaptic cell raising its membrane potential and thus inhibiting it.
This is a fast response — taking only about 1 millisecond.
•Binding of GABA to GABAB receptors activates an internal G protein and a "second messenger" that leads to the opening of nearby potassium (K+) channels. As you might expect, this is a slower response, taking as long as 1 second.
In both cases, the resulting facilitated diffusion of ions (chloride IN; potassium OUT) increases the membrane potential (to as much as −80 mv). This increased membrane potential is called an inhibitory postsynaptic potential (IPSP) because it counteracts any excitatory signals that may arrive at that neuron.
A hyperpolarized neuron appears to have an increased threshold. Actually, the threshold voltage (about −50 mv) has not changed. It is simply a question of whether the depolarization produced by excitatory synapses on the cell minus the hyperpolarizing effect of inhibitory synapses can reach this value or not.
Some neurotransmitters
Acetylcholine (ACh)
Widely used at synapses in the peripheral nervous system. Released at the terminals of
•all motor neurons activating skeletal muscle.
•all preganglionic neurons of the autonomic nervous system
•the postganglionic neurons of the parasympathetic branch of the autonomic nervous system.
Also mediates transmission at some synapses in the brain. These include synapses involved in the acquisition of short-term memory. Drugs that enhance ACh levels — acetylcholinesterase inhibitors — are now used in elderly patients with failing memory (e.g., Alzheimer's patients).
Nicotinic vs. Muscarinic Acetylcholine Receptors
ACh acts on two different types of receptor:
•nicotinic receptors are
◦found at the neuromuscular junction of skeletal (only) muscles,
◦on the post-ganglionic neurons of the parasympathetic nervous system, and
◦on many neurons in the brain (e.g. in the ventral tegmental area).
◦nicotine is an agonist (hence the name)
◦curare is an antagonist (hence its ability to paralyze skeletal muscles)
•muscarinic receptors are
◦found at the neuromuscular junctions of cardiac and smooth muscle as well as on
◦glands, and on
◦the post-ganglionic neurons of the sympathetic nervous system.
◦muscarine (a toxin produced by certain mushrooms) is an agonist.
◦atropine is an antagonist (hence its use in acetylcholinesterase poisoning)
Amino acids
•Glutamic acid (Glu); used at excitatory synapses in the central nervous system (CNS). Essential for long term potentiation (LTP), a form of memory.
Like GABA, Glu acts on two types of CNS synapses:
◦FAST (~1 msec) with Glu opening ligand-gated Na+ channels;
◦SLOW (~1 sec) with Glu binding to receptors that turn on a "second messenger" cascade of
biochemical changes that open channels allowing Na+ into the cell.
•Gamma aminobutyric acid (GABA); used at inhibitory synapses in the CNS (see above).
•Glycine (Gly). Also used at inhibitory synapses in the CNS. In fact, both GABA and glycine are released together at some inhibitory synapses.
Catecholamines
Synthesized from tyrosine (Tyr)
•Noradrenaline (also called norepinephrine). Released by postganglionic neurons of the sympathetic branch of the autonomic nervous system. Also used at certain synapses in the CNS.
•Dopamine. Used at certain synapses in the CNS.
Other monoamines
•Serotonin (also known as 5-hydroxytryptamine or 5HT). Synthesized from tryptophan (Trp).
•Histamine
Both of these neurotransmitters are confined to synapses in the brain. (However, serotonin is also secreted from the duodenum, where it acts in a paracrine manner to stimulate intestinal peristalsis, and as a circulating hormone, where it is taken up by platelets and also suppresses bone formation.)
Peptides
A selection of 8 of the 40 or more peptides that are suspected to serve as neurotransmitters in the brain. The first five also serve as hormones.
•Vasopressin
•Oxytocin
•Gonadotropin-releasing hormone (GnRH)
•Angiotensin II
•Cholecystokinin (CCK)
•Substance P
•Two enkephalins
◦Met-enkephalin (Tyr-Gly-Gly-Phe-Met)
◦Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu)
ATP
ATP — probably along with another neurotransmitter — is released at some synapses in the brain.
Turning Synapses Off
Once its job is done, the neurotransmitter must be removed from the synaptic cleft to prepare the synapse for the arrival of the next action potential. Two methods are used:
•Reuptake. The neurotransmitter is taken back into the synaptic knob of the presynaptic neuron by active transport. All the neurotransmitters except acetylcholine use this method.
•Acetylcholine is removed from the synapse by enzymatic breakdown into inactive fragments. The enzyme used is acetylcholinesterase.
Nerve gases used in warfare (e.g., sarin) and the organophosphate insecticides (e.g., parathion) achieve their effects by inhibiting acetylcholinesterase thus allowing ACh to remain active. Atropine is used as an antidote because it blocks ACh muscarinic receptors.
Drugs and Synapses
Many drugs that alter mental state achieve at least some of their effects by acting at synapses.
GABA Receptors
The GABAA receptor is a ligand-gated chloride channel. Activation of the receptors increases the influx of chloride (Cl−) ions into the postsynaptic cell raising its membrane potential and thus inhibiting it.
A number of drugs bind to the GABAA receptor. They bind at sites different from the spot where GABA itself binds, but increase the strength of GABA's binding to its site. Thus they enhance the inhibitory effect of GABA in the CNS.
These drugs include:
•sedatives like phenobarbital
•anti-anxiety drugs like Alprazolam, Bromazepam,(all members of a group called benzodiazepines)
In view of their common action, it is not surprising that they act additively; taken together (e.g., alcohol and Valium) these drugs can produce dangerous overdoses.
The recreational (and illegal) drug γ-hydroxybutyrate binds to the GABAB receptor.
Catecholamine synapses
Many antidepressant drugs (the so-called tricyclic antidepressants like amitriptyline interfere with the reuptake of noradrenaline and serotonin from their synapses and thus enhance their action at the synapse.
The popular antidepressant fluoxetine , seems to block only the reuptake of serotonin.
Dopamine synapses
One class of dopamine receptor is bound by such drugs as chlorpromazine and haloperidol. Binding of these drugs leads to increased synthesis of dopamine at the synapse and eases some of the symptoms of schizophrenia.
Synapses blocking pain signals
The two enkephalins are released at synapses on neurons involved in transmitting pain signals back to the brain. The enkephalins hyperpolarize the postsynaptic membrane thus inhibiting it from transmitting these pain signals.
The ability to perceive pain is vital. However, faced with massive, chronic, intractable pain, it makes sense to have a system that decreases its own sensitivity . Enkephalin synapses provide this intrinsic pain suppressing system.
Opiates such as
•heroin
•morphine
•codeine
•methadone
bind these same receptors. This makes them excellent pain killers.
However, they are also highly addictive.
•By binding to enkephalin receptors, they enhance the pain-killing effects of the enkephalins.
•A homeostatic reduction in the sensitivity of these synapses compensates for continued exposure to opiates.
•This produces tolerance, the need for higher doses to achieve the prior effect.
•If use of the drug ceases, the now relatively insensitive synapses respond less well to the soothing effects of the enkephalins, and the painful symptoms of withdrawal are produced.
