UNDERSTANDING THE BRAIN: HOW NEURONS COMMUNICATE
During the “Decade of the
Brain,” great strides have been made in understanding how the brain works.
Efforts to develop new drugs for treating psychosis have benefited from greatly
enhanced understanding of how neurons communicate with one another. This
article introduces basic concepts including neurotransmitters (chemical
messengers, receptors) and how cells talk with one another which will lay the
foundation for discussions of how psychotherapeutic drugs work.
NEURONS
The body contains more than 100 billion
neurons. Neurons are similar to other cells in the body in that they have a
cell membrane, a nucleus containing genes, and organelles that carry out basic
cellular functions such as energy production. One important difference is the
presence of extensions that receive messages (dendrites) and transmit messages
(axons)). Although mostly concentrated in the brain, neurons are also important
for both communicating sensory information and controlling body functions such
as muscle activity.
HOW NEURONS COMMUNICATE
Various stimuli such as light, sound,
temperature and pain interact with specific sensory receptors which transform
the stimulus into a neural code that is carried by a chain of neurons to the
brain. Systems of neurons in the brain are then responsible for interpreting
this information -- information processing.
Information is carried along axons and
dendrites by changes in electrical properties called action potential. An
action potential is initiated when a chemical messenger attaches to a specific
site called a receptor. This attachment triggers an electrical signal to be
generated that travels through the neuron. Once the electrical signal reaches
the end of the axon, a neurotransmitter is released into the synaptic cleft,
the gap between neurons. As the neurotransmitter diffuses across the cleft, it
binds with receptor sites on another neuron, initiating another action
potential. This process is repeated and a chain reaction occurs exciting many
neurons in the process.
REGULATING NEUROTRANSMITTER AND RECEPTOR INTERACTION
Once a neurotransmitter has fulfilled
stimulation of a receptor it should be removed from the cleft. This is
accomplished primarily by two processes: 1) Enzymatic degradation
(deactivation) occurs when a specific enzyme changes the neurotransmitter so
that it will no longer be recognized by the receptor. MAO is one such enzyme.
MAO inhibitors (MAOI), such as Nardil, are antidepressants that work by
preventing MAO from deactivating the neurotransmitters. 2) Reuptake, a method
whereby a structure that functions as a pump, recycles the neurotransmitter,
removing it from the cleft. Most anti-depressants work by blocking this
reuptake structure.
NEUROTRANSMITTER-RECEPTOR SYSTEMS AS TARGETS FOR
DRUGS
Each of the components involved in neural
functioning creates a potential target for therapeutic drugs. As discussed
earlier, the re-uptake apparatus is a site of action for many antidepressants.
Antipsychotic drugs act primarily at receptors. There are several receptor
sites specifically for dopamine which are classified into categories based on
structural, pharmacological, and functional characteristics. The main target of
classic antipsychotic drugs is the D2 dopamine receptor. New research has
identified the D4 dopamine receptor, which may have unique functions such as
regulating dopamine production.
The D4 receptor is important because of its
ability to readily bind with the antipsychotic drug clozapine compared with the
other dopamine receptors without producing extrapyramidal symptoms (EPS) such
as dystonia (severe muscle spasms), tremors, lethargy, etc. The D4 receptor is
of interest because it may be a site of action of clozapine. Although clozapine
binds to many well known receptors (dopamine, serotonin, cholinergic,
adrenergic), researchers speculate that its D4 activity may impact its unique
therapeutic characteristics. Consequently, efforts have been made to identify
drugs that act exclusively on the D4 receptor.
Researchers are studying new compounds that
target the dopamine D4 receptor site specifically, using sophisticated animal
experiments. Preliminary results suggest that they may be effective for both
positive (i.e. hallucinations)and negative (i.e. withdrawal) symptoms of
psychotic illnesses without the usual side effects such as movement disorders
(tardive dyskinesia), seizures, and sedation. We look forward to reporting
results as they become available.
Source: MINDVIEW , SUMMER 1999, published by
VA DESERT PACIFIC HEALTHCARE
NETWORK
For more information about Mental
Illnesses -
Contact:
The National Alliance on Mental Illness
NAMI of Greater Chicago
1536 West Chicago Ave, Chicago, IL 60622
Phone: 312-563-0445