Friday, January 28, 2011

More on neuroplasticity


Neuroplasticity: how our brains re-wire.


Researchers have now shown that long-term changes affect the brain even after drug use has ceased. This concept is especially important in light of the revolutionary idea of neuroplasticity, a conception that has overtaken the field of neuroscience in recent years. The overarching concept of neuroplasticity is that our brains are constantly changing and evolving. Whereas scientists in the field once believed that we were born with all of the brain cells that we would have in our entire life, we now understand that neurons are able to regenerate, and even more importantly, that our brain circuits are able to rewire as a result of experience.  Evidence from research of the past two decades offers support for this theory. Thompson showed that patients suffering from aphasia as a result of brain injury were able to regain linguistic functioning by recruiting new areas of the brain that were not typically central to speech contribution to play a key role in language.[1] Melzack et al. showed that human perception of pain is at least partially the result of past experience that causes the brain to rewire following painful stimuli.[2]

However, evidence in favor of neuroplasticity may seem contradictory in light of the argument that drugs have a long-term effect on the brain. After all, if the brain has the ability to change so much, doesn’t this mean that it will recover from any damage that is caused by drug use? Not necessarily. While the brain is able to recover from some degree of insult, the mechanism that causes drug users to experience a euphoric event is also involved in the long-term changes that result from such abuse. According to Uys and Reissner (Glutamatergic Neuroplasticity in Cocaine Addiction, Progress in Molecular Biology and Translational Science. Vol 98. 2011) despite the fact that initially, drugs such as cocaine activate the dopaminergic pleasure system, long term use of drugs causes the brain to recruit new areas to play a role in the mechanism. The authors state:

Over time and with chronic exposure, other structures involving glutamatergic and GABAergic transmission and the brain stress systems are subsequently recruited in latter stages of addiction. For example, key glutamatergic projections are sent from the [pre-frontal cortex], amygdala, and hippocampus, and GABAergic projections are sent from medium spiny neurons of the [nucleus accumbens] core and shell to the vental pallidum and back to the [ventral tegemental area] (371).  

This statement is central to the concept of addiction. Although the individual may enjoy the first time that he or she uses a given drug and may have a strong desire to use the substance again, the real consequences of addiction usually occur as a result of chronic use. This is at least partially due to the rewiring of the pleasure circuits in the brain. However, arguing that using drugs a single time is safe, given the fact that re-wiring cannot occur on the first exposure, is naïve. Although it may take a number of times to do irreparable remodeling of neurocircuitry, it seems clear that the long term changes that occur are not worth the pleasure that may result. Uys and Reissner offer support for this claim, stating, “Long-term potentiation is observed early in the VTA, following acute exposure to drugs of abuse. This LTP lasts at least 5 days following a single drug exposure” (373).






[1] Thompson, C. K. (2000). Neuroplasticity: Evidence from aphasia. J. Commun. Disord., 33, 357-366.
[2] Melzack, R., Coderre, T. J., Katz, J., & Vaccarino, A.L. (2001). Central neuroplasticity and pathological pain. Annals of the New York Academy of Sciences. 933, 157-174.

Thursday, January 27, 2011

"What is the most addictive drug?"-- This and other thoughts on defining addiction

Although the consequences of using and difficulty to rehabilitate from a substance depend on many factors, including frequency and amount of time of use, the drug of choice must be considered. Drugs of abuse include, but are not limited to, marijuana, cocaine, methamphetamine, MDMA (or ecstasy), so-called “club drugs” (GHB, Ketamine, and Rophynol), LSD, phencyclidine, mescaline, heroin, opium, inhalants, anabolic steroids, and prescription drugs such as benzodiazepines and opiates pain medications. According to a 1990-1992 study from the National Comorbidity Survey, it was estimated that among 15-54 year-olds, the most commonly abused illicit drug was marijuana, with 46.3% of individuals responding affirmatively when asked if they had ever used a given substance. However, among users of any given drug, the drug with the highest percentage of dependence among individuals was heroin, with 23.1% of users dependent on the substance.

Before being able to pin down addiction, as defined for a given illicit drug, it is important to define addiction. While individuals disagree about the exact meaning of “addiction” the DSM-IV-TR defines substance abuse, which is the precursor to any form of addiction, as:
A. A maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by one (or more) of the following, occurring within a 12-month period:
1.     Recurrent substance use resulting in a failure to fulfill major role obligations at work, school, or home (e.g., repeated absences or poor work performance related to substance use; substance-related absences, suspensions or expulsions from school; neglect of children or household)
2.     Recurrent substance use in situations in which it is physically hazardous (e.g., driving an automobile or operating a machine when impaired by substance use)
3.     Recurrent substance-related legal problems (e.g., arrests for substance-related disorderly conduct
4.     Continued substance use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the substance (e.g., arguments with spouse about consequences of intoxication, physical fights)
B. The symptoms have never met the criteria for Substance
             Dependence for this class of substance.

Individual drug addictions, referred to by the DSM, as “dependence” are similar among various substance types despite small differences for a given drug. An example is seen in classification of opioid dependency:
            1. A strong desire or sense of compulsion to take the drug;
2. Difficulties in controlling drug-taking behavior in terms of its onset, termination, or levels of use;
3. A physiological withdrawal state when drug use is stopped or reduced, as evidenced by: the characteristic withdrawal syndrome for the substance; or use of the same (or a closely related) substance with the intention of relieving or avoiding withdrawal symptoms;
4. Evidence of tolerance, such that increased doses of the drug are required in order to achieve effects originally produced by lower doses;
5. Progressive neglect of alternative pleasures or interests because of drug use, increased amount of time necessary to obtain or take the drug or to recover from its effects;
6. Persisting with drug use despite clear evidence of overtly harmful consequences, such as harm to the liver, depressive mood states or impairment of cognitive functioning.

The DSM’s sixth point is important, especially for researchers who study drug addiction. Individuals who have a drug addiction are usually aware that their lifestyle choices have negative effects; however, their choice to use the drug despite such consequences is one of the primary characteristics of an addiction. What leads people to continue to intake substances that causes obvious self-harm?

Wednesday, January 26, 2011

Staining and writing

Today has been a day filled with two things, writing my paper and staining sections of rat brain. 


Remember last week when I told you that I cut sections of the rat brain? They look like this after they are mounted on the slide.

This is great and all, but if you leave them like this it will be difficult to see the sections under a microscope to really see what is important. That is why staining is necessary. 

Sections are placed in a variety of different liquids, in an assembly line-ish fashion. I dip the slide in one and leave it in for the appropriate amount of time and then go to the next one. Here is what the solutions look like. 
It reminds me of dying Easter eggs. 
Here is the list of things that must be done to correctly stain each slide.

When completed, the slides turn out beautifully. Here is an example of some of the ones I did.


Now I'm off to do more of what I have been doing today.... Until tomorrow.

Tuesday, January 25, 2011

Why study addiction?


Simply using the term “addiction” in everyday conversation evokes frightening feelings and calls to mind images of drug abusers who have lost everything in life in search of what has become the individual’s only happiness in life. Even using such a term, “happiness,” is a stretch: An addict’s mind is so obsessed with his or her given substance that not having that pleasure forces the individual to face a somber, terrifying, and overall dismal existence. While viewing the repercussions of such destructive chemicals elicits a certain feeling of uneasiness, recent popular culture has harnessed the fears of a nation. The modern American entertainment industry has gone so far as to create an enterprise centered upon the consequences of drug abuse and addiction. Television shows such as HBO’s Addiction, A&E’s Intervention, and VH1’s Celebrity Rehab with Dr. Drew (as well as its Spin-off, Sober House) highlight the effects of drugs in the United States and shed light upon the familial and personal destruction that ensues following an individual’s downward spiral into the world of drug addiction. However, the consequences of drug addiction extend far beyond the lucrative entertainment industry. According to Uys and Reissner,
Addiction to drugs of abuse represents a major worldwide public health concern, affecting all ethnic, racial, and socioeconomic groups. Worldwide 2009 estimates of the number of people with a substance abuse problem range from 18-38 million, while recreational users of illicit drugs are in the range of 172-250 million. Estimated total financial costs of addiction collectively for illegal drug abuse, alcoholism, and nicotine addiction in the United States alone exceed $500 billion annually.

Monday, January 24, 2011

Writing is hard

Unfortunately, I am reporting to you that I have not gotten as much writing done as I should have by this point, so that is the goal of this week. I am going to try to organize some stuff tonight for that, so I hope you will excuse my short post and look forward to longer insights tomorrow. It is hard to believe how fast interim has gone by!

Friday, January 21, 2011

Presentation and Paper

Right now almost everyone that works in the lab is on a tour a new building that could become their home. However, because this site is still under construction, and only 10 people are allowed to go at once, I had to stay here. But that's fine because I can write my post for today.


I need to get started on my presentation and paper for the end of interim. Okay, well I have started on the presentation part of it, and plan on using some of the things I have talked about in my blog in my paper, so I have that going for me. I think what I really need to do, however, is to write a good outline to organize all the points I am going to talk about. I know I'm going to sound like that annoying high school teacher when I say this, but I truly have found that if I write a good outline, a paper will practically write itself. That being said, I hope to start on it this afternoon, unless Kate has some sort of thing she wants me to do. 


On another note, I can't believe that it is Friday and the end of my second week! It's beautiful weather in Charleston today, so maybe I will go on a run this weekend. Well, that's the plan if I can get enough motivation to do it.  Last weekend it was far too cold. Maybe I will even run on the bridge and re-live some Cooper River Bridge Run memories....But that's pretty unlikely, let's be honest. Enjoy your weekend!

Thursday, January 20, 2011

Western Blot and Thursday Activities of Daily Living

Sorry I missed posting yesterday. It was a bit of a crazy day.

This morning when I got to the lab, Kate was preparing for a scheduled kill. Unfortunately, the lab rats cannot live forever, and as a result, they must eventually die. I know this might seem very sad, but it is important to remember several things. First of all, if it wasn't for the purposes of science, then these rats wouldn't have been born in the first place. Secondly, this is a fact that goes along with this type of animal research. Lastly, and fortunately, although the rats must be killed, the researchers in the lab make every effort for their death to be as quick and painless as possible. That is exactly what I saw today, and I can report to you that no rat was stressed out before its death. 

The rest of the day was spent confirming that I did not have TB, finishing up some training for OSHA, and learning about a Western Blot. Wikipedia:

The Western blot (alternatively, protein immunoblot) is an extremely useful analytical technique used to detect specific proteins in the given sample of tissue homogenate or extract. It uses gel electrophoresis to separate native or denatured proteins by the length of the polypeptide (denaturing conditions) or by the 3-D structure of the protein (native/ non-denaturing conditions). The proteins are then transferred to a membrane (typically nitrocellulose orPVDF), where they are probed (detected) using antibodies specific to the target protein.[2][3]


A western blot's name comes from the fact that the first sort of immunoblotting technique 
was invented by a man of the last name Southern. This allowed scientists to detect DNA. 
Just to be witty, the scientists who invented the technique for detecting RNA decided to call 
the stain a Northern blot. Similarly, the Western blot was named to play on these already 
established techniques.


Step 1:


Step 2:


Step 3:


Step 4:

And lastly: