July 15, 2016

A recent study of the Substance Abuse and Mental Health Services Administration found that 16% of adult Americans used drugs in one form or another. If you compare these figures with the statistics on psychiatric illnesses, it is clear that only a fraction of those who have used drugs become fully dependent on them, but why not? Can some people be more or less at risk of substance abuse?

The likelihood that some people are more accustomed to addiction brings us back to the psychological concept that people with a more impulsive character and a developed desire to experience sensations (for example, attending swinger parties) are more at risk of becoming addicts than others. Modern research has found the biological roots of this idea, which is not only relevant to humans.

Many people are surprised to think that rats have certain elements of personality, but they do. Natural genetic changes in highly developed animals make it possible for different individuals’ brains to evolve with some differences. As a result, some individuals may develop behaviors different to others. 

Study of addictive rat behaviour

Prior to the experiment, the rats in the colonies had been trained to poke their noses at a specific spot in the cage in order to obtain an instant discharge of cocaine in the body. Besides, the cocaine was served only with the lights on. For the first 20 seconds, when the rats were experiencing the peak of sensation, the area on the wall where they were pointing their noses was illuminated to help them assess the formation of the addiction later. The results showed that the rat scouts were more likely to be long-term addicts to cocaine. How did you figure that out?

It was the rat scouts that showed the problem. The longer the experiment lasted, the less these animals could restrain themselves from pointing their noses at the wall, even in the absence of light. It should be noted that rats clearly understood that they could not obtain cocaine in the absence of light, as they had previously drawn attention to this factor. However, the longer the animals received cocaine, the less they could restrain themselves. In addition, only the rats from the intelligence colony began to behave this way, while the calmer individuals were removed from the drug-receiving area when the lights were off. 

The researchers further found that the rat scouts were also more likely to relapse after abstinence. So the rats from both colonies were relocated, and then a month later, they were returned to the same cage where they used to get cocaine. The light in the cell switched on, indicating the availability of the drug (although it was not injected when activated), and when individuals were poked through the wall to receive a dose of the drug, the area was lit, as in the previous experiment. In this cell, the rat scouts showed a greater propensity for recidivism than their more relaxed friends. The scouts continued to poke the site to activate cocaine injection four times more frequently than other individuals, although these actions did not have the desired effect.

Gene activity of dependent individuals 

The intelligence rats’ behavioral model showed that they had something like an addictive personality. In order to understand how this phenomenon is explained at the biological level, researchers have studied the brain activity of addicted rats who have been using cocaine for a long time or have had no experience of using it.

Researchers have focused on a cluster of neurons called the nucleus accumbens, an element of the brain’s reward system that absorbs large amounts of dopamine when consuming sugar, having sex, or using drugs like cocaine and amphetamines. It has long been known that this system plays a key role in shaping the desire for something, even if the brain does not enjoy it. It is logical to assume that it is the dopamine system that plays an important role in the development of the pathological desire characteristic of dependence. So scientists have found out whether the gene activity of brain cells from nucleus accumbens is different from that of stable individuals.

Effect of the dopamine system on dependency formation

Studies have shown that confirmed rat relationships, even those with no experience of cocaine using, are characterized by the weak activity of the gene responsible for the formation of the dopamine receptor of a specific type, the D2 receptor.

Receptors are known to be tiny proteins that excite brain cell membranes by capturing molecules of chemicals produced by other neurons and triggering reactions to these substances. Thanks to the receptors, brain cells can transmit signals using chemical compounds. Receptors can perform different functions depending on their location. This also applies to D2 receptors, which are located near dopamine-producing cells, where they can track dopamine levels in the environment and, if necessary, stop further release by the neuron to prevent neurochemical build-up.

Then, scientists discovered some features of histone proteins that are found in parts of D2 in dependent rats. These proteins had a specific label that suppresses gene activity: the marker causes proteins to accumulate so tightly around DNA that the gene becomes simply inaccessible to the elements of the cell that it takes to start producing the protein. 

Practically, the overwhelming marker in the portions of the D2 gene means that in dependent rats this gene is simply not read, which explains its low activity. The fact that this feature is also present in rats with no history of cocaine use suggests that marker appears early in life and may be one of the reasons why these individuals react differently to cocaine than more stable rats. Interestingly, rats with the strongest connection between the suppressant marker and the D2 gene are the most likely to relapse after prolonged abstinence. 

Further studies have shown that independent rat brain cells, there are more active genes for FGF2 protein coding. Again, this feature has been observed in both individuals with no history of cocaine use and those who have used the drug for a long time. It is very likely that the active FGF2 gene is another feature of the brain-dependent individual. 

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