Nerve Function and Drug Action: Simplified
CELL SITES OF DRUG ACTION
(A CARTOON VERSION OF HOW
CELLS TALK TO EACH OTHER)
*These sections cannot be printed or down-loaded without permission of the
Director: Carlton Erickson, Director
Basic Nerve Function
(This is a 2-minute course in Neurophysiology!)
- There are millions of cells in the brain. This picture depicts two nerve cells (neurons)
and their important components. Nerve Cell One is on the top, Nerve Cell Two is on the bottom.
The large portion of Nerve Cell One is the working part of the cell, also known as the
presynaptic area. The presynaptic area is at the end of a sending fiber called an axon, which
begins outside the boundaries of the picture in a cell body called the soma. Inside the soma
are manufacturing chemicals known as enzymes that manufacture chemicals called neurotransmitters.
These neurotransmitters pass down the axon under the influence of a small electrical
current called an action potential. The neurotransmitters are packaged in what look like
cellophane envelopes (called vesicles). These vesicles release their contents (neurotransmitters)
into the space between the two cells (the synapse), under the influence of small concentrations
of calcium ions.
Once in the synapse, one of four things can happen to the neurotransmitters.
1) activate an excitatory receptor (on the left), causing Nerve Cell Two to be more likely to fire,
2) activate an inhibitory receptor (middle), causing Nerve Cell Two to be less likely to fire,
3) are "gobbled up" (metabolized) by a monster enzyme (right), or
4) are taken back up into Nerve Cell One (reuptake), repackaged, and sent on down the nerve
cell for use later on.
Inside Nerve Cell One is another monster enzyme, known as MAO, which gobbles up
the neurotransmitter molecules that accidentally leak out of the vesicles. Outside and
above the nerve membrane is a small molecule known as chloride ion, which is necessary
for the proper integrity of the vesicle membrane.
Under each of the receptor "ghosts" is a small rectangle containing globules
of substances known as G proteins that are the beginning of a chemical and electrical
cascade of events that make Nerve Cell Two more likely (excitation) or less likely
(inhibition) to fire and carry the message of Nerve Cell One to the next nervous system component.
Where a Few Drugs Work
- Cocaine - It is now known that cocaine acts at the receptor site on
Nerve Cell One where reuptake occurs. This is known as the dopamine transporter
(abbreviated DAT). Cocaine blocks DAT to cause an increase in dopamine in the
synapse, producing the events that eventually lead to the stimulation that is
characteristic of cocainežs pharmacological actions.
Amphetamines - Amphetamines act differently than cocaine, because
they cause an increased release of dopamine (and to some extent other
neurotransmitters such as norepinephrine and serotonin). The end result
is more dopamine in the synapse (like cocaine), but amphetamine has a more
complex pharmacology and works on slightly different brain areas so that
its pharmacology is different than that of cocaine.
When either cocaine or amphetamines act on the pleasure pathway
of the brain (known as the medial forebrain bundle), the result is a pleasurable
or euphoric feeling. When these drugs act on other parts of the brain, other
things happen, such as increased muscle movement, jitteriness, increased
talkativeness, and even hallucinations. So the part of the brain that is
affected by the drug determines the pharmacological actions and side effects,
in spite of the fact that the drug works on the same place on the cell in every part of the brain!
Drugs like Prozac work in a fashion similarly to cocaine, but with
two main differences. Prozac is a Selective Serotonin Reuptake Inhibitor (SSRI),
meaning that it blocks only the uptake of serotonin at the serotonin transporter
(SERT). This leads to an increase in serotonin in the synapse to overcome clinical
depression. So it works on a different neurotransmitter than cocaine. Also, Prozac
acts throughout the limbic system of the brain, which is where we feel our emotions.
It does not have a specific and powerful action on the pleasure pathway, which is why
it is not addicting. We assume, then, that for something to be able to produce
addiction, it must have a major action on the pleasure pathway.
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For further information, please write or call:
Addiction Science Research and Education Center
Carlton Erickson, Director
The College of Pharmacy
UT Austin, Austin TX
14 November 2012