Andi
01-18-06, 04:50 AM
<i>You're taking Prozac, and you've heard it described as an SSRI. Maybe you know that SSRI stands for Selective Serotonin Reuptake Inhibitor. But that's quite a mouthful - what does it mean?</i></p><p>
<font face="verdana, geneva, helvetica" size="2">In the coming weeks and months we will be looking at several medications that are commonly prescribed for mood disorders such as manic depression. Included in these reviews will be a look at how each functions - or is thought to function, since many are still being studied. We will also take an in-depth look at why so many of these drugs cause weight gain - a subject of importance to an all-too-large percentage of people who take psychiatric medications.</font></p><font face="verdana, geneva, helvetica" size="2">In order to make sense of any of this, it is necessary to understand something about how impulses are transferred from one nerve to the next, because medications such as mood stabilizers, antidepressants and antipsychotics all affect this process to bring about changes. In this article I will give a brief simplified description of how the brain's message carriers, called "neurotransmitters," operate, and then try to clarify the process by telling the illustrated story, "GABAs in the 'Hood."*</font><p>
<font face="verdana, geneva, helvetica" size="2"><b>Neurotransmitters</b></font></p><p>
<font face="verdana, geneva, helvetica" size="2">There are several of these, but the ones that are most concerned with mood disorders are:
</font></p><ol>
<font face="verdana, geneva, helvetica" size="2"><li>The monoamines - serotonin, norepinephrine and dopamine;
</li><li>GABA (Gamma amino butyric acid); and
</li><li>Glutamate
</li></font></ol>
<font face="verdana, geneva, helvetica" size="2">Others that come into play with some side effects are acetylcholine, which transmits orders to the muscles, and histamine, which has a lot to do with allergies but also affects sleep.</font><p>
<font face="verdana, geneva, helvetica" size="2">When a message comes in at one end of a nerve cell, an electrical impulse travels down the "tail" of the cell, called the axon, and causes the release of the appropriate neurotransmitter. Molecules of the neurotransmitter are sent into the tiny space between nerve cells, called the synaptic cleft. There, one or more of six things can occur for each molecule:
</font></p><ol>
<font face="verdana, geneva, helvetica" size="2"><li>It may "bind" (attach) to the receptors in the adjacent nerve cell, sending the message on, then leave the receptor, repeat Step 1, or go on to one of the other steps;
</li><li>It may hang around in the synapse until a receptor becomes available, and then bind to it, release, and continue with Steps 1-3 until its activity is ended by Step 4, 5 or 6;
</li><li>It may bind (attach) to the first cell's autoreceptors, which tell that cell not to release any more of the neurotransmitter molecules, then leave the autoreceptor and continue trying to bind again somewhere until its activity is ended by Step 4, 5 or 6;
</li><li>It may be rendered inactive by an enzyme;
</li><li>It may be reabsorbed by the first cell in the "reuptake" process, and recycled for later use or deactivated there; or
</li><li>It may diffuse out of the synapse and be deactivated elsewhere.
</li></font></ol>
<font face="verdana, geneva, helvetica" size="2">Now, so many things can go wrong with this process that it's not surprising mood disorders are fairly common. For example:
</font><ol>
<font face="verdana, geneva, helvetica" size="2"><li>The nerve cells (neurons) might not be manufacturing enough of a neurotransmitter
</li><li>Too many molecules of the neurotransmitter are being dissolved or deactivated by enzymes
</li><li>Too much of a neurotransmitter is being released
</li><li>The molecules are being reabsorbed too quickly by the reuptake transporters
</li><li>The autoreceptors are being activated too soon, shutting down the release of neurotransmitter molecules prematurely
</li></font></ol>
<font face="verdana, geneva, helvetica" size="2">Or there could be some other circumstance involving electrically charged particles of potassium, sodium, chloride or calcium. <font color="#0000a0">It's enough to make your head hurt, isn't it?</font></font><p>
<font face="verdana, geneva, helvetica" size="2">Here, let's look at it another way.</font></p><p>
<font face="verdana, geneva, helvetica" size="2"><b>Communication at Brain Complex, or<br>
"GABAs in the 'Hood"</b></font></p><p>
<font face="verdana, geneva, helvetica" size="2">To start with, look at Figure 1, which is a very simplified drawing of a synapse.</font></p><p>
<font face="verdana, geneva, helvetica" size="2"><b>Figure 1</b><br>
<img src="http://bipolar.about.com/library/graphics/synapse1.gif" alt="Synapse, vesicles, autoreceptors, terminal button, axon and enzyme" height="400" width="400"></font></p><p>
<font face="verdana, geneva, helvetica" size="2"><b>Figure 2</b><br>
<img src="http://bipolar.about.com/library/graphics/synapse2.gif" alt="A call is received by the motor pool" align="left" height="233" width="233">For our story let's change the components shown above into something more familiar. The two neurons are Building A and Building B of Brain Complex, separated by a narrow street ("the 'hood," the synaptic cleft). The GABA terminal button is now a motor pool. Each vesicle containing neurotransmitter molecules becomes a minibus filled with GABA Team messengers. The receptors and autoreceptor become phone booths. The reuptake transporter, where neurotransmitters are sucked back in to be recycled, changes to an inviting coffee shop. And the enzymes are assassins on motorcycles. (No offense meant to motorcycle lovers!)</font></p><p>
<font face="verdana, geneva, helvetica" size="2">So over in Building A, the driver of each minivan gets a call from the front office (that's the neuron's cell body, not shown) on his cell phone: "Send this Message over to Building B!" And right away things start to happen.</font></p><p>
<table align="right" border="0" cellpadding="0" cellspacing="0"><tbody><tr><td align="right"><font face="verdana, geneva, helvetica" size="2">
<b>Figure 3</b><br>
<img src="http://bipolar.about.com/library/graphics/synapse3.gif" alt="The vesicles release neurotransmitters into the synaptic cleft" height="233" width="233"></font></td></tr></tbody></table>
<font face="verdana, geneva, helvetica" size="2">
Immediately the drivers take their vehicles (that is, vesicles) to the garage exit and release the GABA Team messengers (neurotransmitters) into the street (synaptic cleft) between Building A (the sending neuron) and Building B (the receiving neuron).</font></p><p>
<font face="verdana, geneva, helvetica" size="2">Like sprinters the GABAs take off quickly, each looking for a phone booth that matches his or her uniform (they could not get into any other color booth). Gertrude, Gerald and Gloria get there first. Quickly each slips into a booth (Figure 4) and makes a call into the office (cell body) of Building B, relaying the Message. Then each backs out and looks for another booth. All the GABA messengers are elbowing each other out of the way (and dodging motorcycles) to get into the available booths, and all make the same call if they get in.</font></p><p>
<font face="verdana, geneva, helvetica" size="2"><b>Figure 4</b><br>
<img src="http://bipolar.about.com/library/graphics/synapse4.gif" alt="Autoreceptors, enzymes, receptors and reuptake transporters" align="left" height="233" width="233">But there are some traps and hazards for the GABA team. George GABA never makes it to Building B at all - he has been knocked unconcscious by a motorcycle-riding Assassin (enzyme). His color change denotes that he has forgotten the Message now - in essense, he has been "deactivated."</font></p><p>
<font face="verdana, geneva, helvetica" size="2">Meanwhile, Glenn GABA has gone to the phone booth attached to Building A. "There's too many of us out here," he tells the front office. "Don't send any more." Then he, too, goes back out into the street. When the front office gets enough similar calls, the minivan drivers will be told to return to the motor pool and not send any more messengers out.</font></p><p>
<font face="verdana, geneva, helvetica" size="2">And then there is that seductive coffee shop (reuptake transporter) on the other corner of Building A. If a messenger gets close enough to smell the heavenly aroma of fresh coffee and doughnuts, he or she will surely be sucked in, and once inside, will be refreshed and then return to the motor pool to await the next assignment. Eventually all the surviving GABAs will return home via the coffee shop.</font></p><p>
<font face="verdana, geneva, helvetica" size="2"><font color="#408080"><b>The whole event has taken no more than a millisecond.</b></font></font></p><p>
</p><hr align="center" size="2" width="300"><p>
<font face="verdana, geneva, helvetica" size="2">Now as you have probably realized, it isn't really this simple. But this illustration will give you a basic idea of how neurotransmitters operate, and why it is so important that they operate correctly, with neither too many nor too few of them being released into the cleft, the autoreceptors and enzymes working properly, and myriad other factors all contributing to a healthy process. When they don't, you can get illnesses like Parkinson's, which has a dopamine deficiency; or you may have tetanus, which prevents the release of GABA and can be fatal if breathing muscle control is therefore lost. Or you might have schizophrenia, which is thought to be caused by too much dopamine, or epilepsy, apparently caused in part by an overabundance of GABA.
Soon we will begin to look at individual medications and medication types used in the treatment of bipolar disorder, including lithium, depakote, SSRI and tricyclic antidepressants, tegretol, antipsychotics and more. Those articles will include information about specific neurotransmitters and receptors. My goal with "GABAs in the 'Hood" has been to provide an easy-to-understand description of basic neurotransmitter functions. Remember the Team messengers and their adventures in the 'hood as you read future articles!</font>
http://bipolar.about.com/cs/neurotrans/l/aa0007_msngrs.htm
<font face="verdana, geneva, helvetica" size="2">In the coming weeks and months we will be looking at several medications that are commonly prescribed for mood disorders such as manic depression. Included in these reviews will be a look at how each functions - or is thought to function, since many are still being studied. We will also take an in-depth look at why so many of these drugs cause weight gain - a subject of importance to an all-too-large percentage of people who take psychiatric medications.</font></p><font face="verdana, geneva, helvetica" size="2">In order to make sense of any of this, it is necessary to understand something about how impulses are transferred from one nerve to the next, because medications such as mood stabilizers, antidepressants and antipsychotics all affect this process to bring about changes. In this article I will give a brief simplified description of how the brain's message carriers, called "neurotransmitters," operate, and then try to clarify the process by telling the illustrated story, "GABAs in the 'Hood."*</font><p>
<font face="verdana, geneva, helvetica" size="2"><b>Neurotransmitters</b></font></p><p>
<font face="verdana, geneva, helvetica" size="2">There are several of these, but the ones that are most concerned with mood disorders are:
</font></p><ol>
<font face="verdana, geneva, helvetica" size="2"><li>The monoamines - serotonin, norepinephrine and dopamine;
</li><li>GABA (Gamma amino butyric acid); and
</li><li>Glutamate
</li></font></ol>
<font face="verdana, geneva, helvetica" size="2">Others that come into play with some side effects are acetylcholine, which transmits orders to the muscles, and histamine, which has a lot to do with allergies but also affects sleep.</font><p>
<font face="verdana, geneva, helvetica" size="2">When a message comes in at one end of a nerve cell, an electrical impulse travels down the "tail" of the cell, called the axon, and causes the release of the appropriate neurotransmitter. Molecules of the neurotransmitter are sent into the tiny space between nerve cells, called the synaptic cleft. There, one or more of six things can occur for each molecule:
</font></p><ol>
<font face="verdana, geneva, helvetica" size="2"><li>It may "bind" (attach) to the receptors in the adjacent nerve cell, sending the message on, then leave the receptor, repeat Step 1, or go on to one of the other steps;
</li><li>It may hang around in the synapse until a receptor becomes available, and then bind to it, release, and continue with Steps 1-3 until its activity is ended by Step 4, 5 or 6;
</li><li>It may bind (attach) to the first cell's autoreceptors, which tell that cell not to release any more of the neurotransmitter molecules, then leave the autoreceptor and continue trying to bind again somewhere until its activity is ended by Step 4, 5 or 6;
</li><li>It may be rendered inactive by an enzyme;
</li><li>It may be reabsorbed by the first cell in the "reuptake" process, and recycled for later use or deactivated there; or
</li><li>It may diffuse out of the synapse and be deactivated elsewhere.
</li></font></ol>
<font face="verdana, geneva, helvetica" size="2">Now, so many things can go wrong with this process that it's not surprising mood disorders are fairly common. For example:
</font><ol>
<font face="verdana, geneva, helvetica" size="2"><li>The nerve cells (neurons) might not be manufacturing enough of a neurotransmitter
</li><li>Too many molecules of the neurotransmitter are being dissolved or deactivated by enzymes
</li><li>Too much of a neurotransmitter is being released
</li><li>The molecules are being reabsorbed too quickly by the reuptake transporters
</li><li>The autoreceptors are being activated too soon, shutting down the release of neurotransmitter molecules prematurely
</li></font></ol>
<font face="verdana, geneva, helvetica" size="2">Or there could be some other circumstance involving electrically charged particles of potassium, sodium, chloride or calcium. <font color="#0000a0">It's enough to make your head hurt, isn't it?</font></font><p>
<font face="verdana, geneva, helvetica" size="2">Here, let's look at it another way.</font></p><p>
<font face="verdana, geneva, helvetica" size="2"><b>Communication at Brain Complex, or<br>
"GABAs in the 'Hood"</b></font></p><p>
<font face="verdana, geneva, helvetica" size="2">To start with, look at Figure 1, which is a very simplified drawing of a synapse.</font></p><p>
<font face="verdana, geneva, helvetica" size="2"><b>Figure 1</b><br>
<img src="http://bipolar.about.com/library/graphics/synapse1.gif" alt="Synapse, vesicles, autoreceptors, terminal button, axon and enzyme" height="400" width="400"></font></p><p>
<font face="verdana, geneva, helvetica" size="2"><b>Figure 2</b><br>
<img src="http://bipolar.about.com/library/graphics/synapse2.gif" alt="A call is received by the motor pool" align="left" height="233" width="233">For our story let's change the components shown above into something more familiar. The two neurons are Building A and Building B of Brain Complex, separated by a narrow street ("the 'hood," the synaptic cleft). The GABA terminal button is now a motor pool. Each vesicle containing neurotransmitter molecules becomes a minibus filled with GABA Team messengers. The receptors and autoreceptor become phone booths. The reuptake transporter, where neurotransmitters are sucked back in to be recycled, changes to an inviting coffee shop. And the enzymes are assassins on motorcycles. (No offense meant to motorcycle lovers!)</font></p><p>
<font face="verdana, geneva, helvetica" size="2">So over in Building A, the driver of each minivan gets a call from the front office (that's the neuron's cell body, not shown) on his cell phone: "Send this Message over to Building B!" And right away things start to happen.</font></p><p>
<table align="right" border="0" cellpadding="0" cellspacing="0"><tbody><tr><td align="right"><font face="verdana, geneva, helvetica" size="2">
<b>Figure 3</b><br>
<img src="http://bipolar.about.com/library/graphics/synapse3.gif" alt="The vesicles release neurotransmitters into the synaptic cleft" height="233" width="233"></font></td></tr></tbody></table>
<font face="verdana, geneva, helvetica" size="2">
Immediately the drivers take their vehicles (that is, vesicles) to the garage exit and release the GABA Team messengers (neurotransmitters) into the street (synaptic cleft) between Building A (the sending neuron) and Building B (the receiving neuron).</font></p><p>
<font face="verdana, geneva, helvetica" size="2">Like sprinters the GABAs take off quickly, each looking for a phone booth that matches his or her uniform (they could not get into any other color booth). Gertrude, Gerald and Gloria get there first. Quickly each slips into a booth (Figure 4) and makes a call into the office (cell body) of Building B, relaying the Message. Then each backs out and looks for another booth. All the GABA messengers are elbowing each other out of the way (and dodging motorcycles) to get into the available booths, and all make the same call if they get in.</font></p><p>
<font face="verdana, geneva, helvetica" size="2"><b>Figure 4</b><br>
<img src="http://bipolar.about.com/library/graphics/synapse4.gif" alt="Autoreceptors, enzymes, receptors and reuptake transporters" align="left" height="233" width="233">But there are some traps and hazards for the GABA team. George GABA never makes it to Building B at all - he has been knocked unconcscious by a motorcycle-riding Assassin (enzyme). His color change denotes that he has forgotten the Message now - in essense, he has been "deactivated."</font></p><p>
<font face="verdana, geneva, helvetica" size="2">Meanwhile, Glenn GABA has gone to the phone booth attached to Building A. "There's too many of us out here," he tells the front office. "Don't send any more." Then he, too, goes back out into the street. When the front office gets enough similar calls, the minivan drivers will be told to return to the motor pool and not send any more messengers out.</font></p><p>
<font face="verdana, geneva, helvetica" size="2">And then there is that seductive coffee shop (reuptake transporter) on the other corner of Building A. If a messenger gets close enough to smell the heavenly aroma of fresh coffee and doughnuts, he or she will surely be sucked in, and once inside, will be refreshed and then return to the motor pool to await the next assignment. Eventually all the surviving GABAs will return home via the coffee shop.</font></p><p>
<font face="verdana, geneva, helvetica" size="2"><font color="#408080"><b>The whole event has taken no more than a millisecond.</b></font></font></p><p>
</p><hr align="center" size="2" width="300"><p>
<font face="verdana, geneva, helvetica" size="2">Now as you have probably realized, it isn't really this simple. But this illustration will give you a basic idea of how neurotransmitters operate, and why it is so important that they operate correctly, with neither too many nor too few of them being released into the cleft, the autoreceptors and enzymes working properly, and myriad other factors all contributing to a healthy process. When they don't, you can get illnesses like Parkinson's, which has a dopamine deficiency; or you may have tetanus, which prevents the release of GABA and can be fatal if breathing muscle control is therefore lost. Or you might have schizophrenia, which is thought to be caused by too much dopamine, or epilepsy, apparently caused in part by an overabundance of GABA.
Soon we will begin to look at individual medications and medication types used in the treatment of bipolar disorder, including lithium, depakote, SSRI and tricyclic antidepressants, tegretol, antipsychotics and more. Those articles will include information about specific neurotransmitters and receptors. My goal with "GABAs in the 'Hood" has been to provide an easy-to-understand description of basic neurotransmitter functions. Remember the Team messengers and their adventures in the 'hood as you read future articles!</font>
http://bipolar.about.com/cs/neurotrans/l/aa0007_msngrs.htm