Rats Teach. Science is learning more about the How and Why of drug abuse. Are you broken?

=============================================================

In ScienceNOW Daily News, for March 1, 2007, Contributing Correspondent, Mary Beckman, in a news article, Just Doob It writes about Jeffrey Dalley, University of Cambridge, United Kingdom, and experiments there in behavior and drug addiction.

Beckman writes, that in movies, drug addicts rarely think twice before pulling a knife on someone or robbing a liquor store. Do drugs make them impulsive? Or do they do drugs because they are impulsive? It may not matter to the script writer, director or producer, but there seems to be a certain accuracy in the 'fictional' portrayal.

With a natural interest in the way the world works, you could only wonder about the veracity of a stereotypical Hollywood movie or made for TV presentation, and the drug addict behavior as portrayed. Maybe you have seen it in person. Maybe there is truth in the characterization, but which is cause, and which is result?

Beckman points it out: A new study in rats suggests that hastiness comes first, and that people may "self-medicate" to curb their rash tendencies.

According to Beckman, drug users tend to be impulsive, but it's not clear why. Some research has shown that impetuous rats also use more cocaine than more calculating rodents, suggesting impulsiveness can lead to drug use. And researchers have found that addicts have fewer D2/3 receptors in their brains. These molecules are involved in the body's reward system, and in monkeys, they decline in response to cocaine use. Because the link between impulsive behavior and drug use is so strong, neuroscientist Jeffrey Dalley of the University of Cambridge, U.K., wondered if the D2/3 receptors might connect the two.

To find out, Dalley and colleagues trained 100 rats to watch a bank of five lights. Every five seconds, one light flashed on, at which point the rats would poke at a hole underneath the lit light and get a food treat. The more impulsive rats tried to "predict" which light would come on, poking at random holes before the light show began and making twice as many mistakes as their patient peers. It turned out that impulsive rats had half as many D2/3 receptors as the even-tempered rats in an area of the brain known to be involved in drug addiction.

[At this point you have some mistake-making impulsive rats, and some rats that are not so impulsive, and not driven to make mistakes. That is, you have two clear bahaviors and two groups of rats exhibiting those behaviors -- and there is a physiological difference -- being the D2/3 receptors being diminished in the "rash" rats, and fully arrayed and normally receptive in the patient "calm and cool" rats.]

So now: Enter The Brain of a Rat on Drugs! With two groups, differentiated . . .

Beckman further describes the experiment.

The researchers then took eight rats from each group and allowed them to eat as much cocaine as they wanted. The impulsive rats consumed nearly twice as much cocaine as the patient rats, the team reports in Science, 2 March 2007.[Nucleus Accumbens D2/3 Receptors Predict Trait Impulsivity and Cocaine Reinforcement. Jeffrey W. Dalley, et. al.] After a week of sobriety, however, the rash rats performed just like the patient rats in the light experiment.

The findings not only show that impulsivity precedes drug use--and that D2/3 receptors are involved--says Dalley, but they also indicate that drug use itself may be a way for animals to regulate their impulsive tendencies. As such, drug treatment programs may benefit from reducing impulsive behavior, he says.

Psychobiologist Marilyn Carroll of the University of Minnesota in Minneapolis says the work is important because it connects the increased drug use of impulsive animals to neurochemistry in the brain, which is impossible to sort out in the complicated world of human drug addicts. She hopes such work will lead to ways to predict who will become a drug addict so predisposed individuals can be trained to prevent drug use.

===================================================

The ScienceNews daily report ends there. The "Nucleus Accumbens . . ."report in Science referenced is, itself. well worth reading and technical. The essence is captured by Beckman as I have quoted and reported here.

Perhaps this physiological based neurochemical link between impulsivness, risk-taking, novelty-experiencing behavior leading to drug use and abuse can be understood and those predisposed to some form of drug addiction "trained" to prevent drug use? They say the human mind is a powerful governor of behavior. However, the seat of this abuse is at a very deep level in all mammal brains; it is at a primal level, and hard to overcome.

One superficial thought would be: Well! If the problem's source is physiological, as in this case of reduced capacity receptors or missing receptors, maybe treatment will not involve so much 'training' as a different therapy involving an approach to the receptor differences, and behavior chemically modulated and moderated under some non-abusive protocols. Maybe eventually we will learn how to reverse the drug bindings or remove them. But it is obviously more than that.

This is a complex area, worthy of medical and scientific pursuit, and I am going to touch on that below.

=====================

A good source for much of what you want to know is the government site:

http://www.drugabuse.gov/

Many drugs act to interfere with brain function in the same way cocaine does. For that it is worth gaining an understanding. These processes are usually irreversible, or difficult to repair or correct. There seem to be limits from which a return is impossible.

Cocaine in the brain — In the normal communication process, dopamine is released by a neuron into the synapse, where it can bind with dopamine receptors on neighboring neurons. Normally, dopamine is then recycled back into the transmitting neuron by a specialized protein called the dopamine transporter. If cocaine is present, it attaches to the dopamine transporter and blocks the normal recycling process, resulting in a buildup of dopamine in the synapse, which contributes to the pleasurable effects of cocaine.

When Dr. Nora Volkow was at NIDA's Regional Neuroimaging Center at Brookhaven National Laboratory in Upton, New York, she provided visual evidence to confirm this theory of how cocaine blocks the reuptake of dopamine. Dr. Volkow used brain images to show that, in cocaine addicts, dopamine is directly involved in the euphoria that reinforces the drug abuser's desire to take drugs.

"The results affirm the theory that dopamine transporter blockade plays a crucial role in the rewarding and reinforcing properties of cocaine in humans," she says, adding that this role may explain why cocaine addicts sometimes binge uncontrollably.

Dr. Volkow theorizes that cocaine binging may result from the corruption of primeval survival-of-the-species urges that are controlled by dopamine.

Dopamine activity is known to control urges to begin - and to repeat - acts that are necessary for survival such as eating, drinking, and engaging in sex. Satisfying these urges results in pleasure or gratification. "Pleasure is a natural reinforcer to increase the probability that a species will engage in a given behavior and continue that behavior," she says. Once these urges have been satisfied, the body's normal response is satiety or "that's enough."

Repeated cocaine use, however, turns "off" this normal satiety response so that users continue craving, and continue drug seeking behavior, she suggests. This short-circuiting of the satiety response could explain why cocaine abusers binge even in the face of powerful negative side effects, she adds.

"When satiety is suppressed, the pleasurable properties of cocaine serve as a trigger for activating brain pathways that will then maintain the drug-consuming behavior," she concludes.

A great amount of research has been devoted to understanding the way cocaine produces its pleasurable effects, and the reasons it is so addictive. One mechanism is through its effects on structures deep in the brain. These deep areas are primal, and primitive, and powerful in influencing behavior.

Scientists have discovered regions within the brain that are stimulated by rewards. One neural system that appears to be most affected by cocaine originates in a region located deep within the brain called the ventral tegmental area (VTA). Nerve cells originating in the VTA extend to the region of the brain known as the nucleus accumbens, one of the brain’s key areas involved in reward.

In studies using animals, for example, all types of rewarding stimuli, such as food, water, sex, and many drugs of abuse, cause increased activity in the nucleus accumbens.

Of course, there is a fatal downside.

The short-term physiological effects of cocaine include constricted blood vessels; dilated pupils; and increased temperature, heart rate, and blood pressure. Large amounts (several hundred milligrams or more) intensify the user’s high, but may also lead to bizarre, erratic, and violent behavior. These users may experience tremors, vertigo, muscle twitches, paranoia, or, with repeated doses, a toxic reaction closely resembling amphetamine poisoning. Some users of cocaine report feelings of restlessness, irritability, and anxiety. In rare instances, "sudden death" can occur on the first use of cocaine or unexpectedly thereafter. Cocaine-related deaths are often a result of cardiac arrest or seizures followed by respiratory arrest.

These downside events are all actually avoidable. The brain training needs to take place before there is an addiction, or even an exposure.