Addiction Science Research and Education Center
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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


cartoon of cell communication

  1. 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.

  2. 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.

  3. 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.

  4. Once in the synapse, one of four things can happen to the neurotransmitters. They either 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.

  5. 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.

  6. 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.

(This is a 2-minute course in Neurophysiology!)


Where a Few Drugs Work

  1. 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.

  2. 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.

  3. 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!

  4. 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
78712-1074
512.471.5198

14 November 2012