The Addicted Brain (18 page)

Although only part of the early life stress story has been described here, many studies from other laboratories support these findings. Surprisingly, these findings are not always well appreciated. Even pharmacology textbooks do not describe how early life factors can alter the response to drugs in adulthood. It is remarkable how our childhood environment can shape a variety of behavior when we are adults. We can guess that the early life stressors cause changes in gene expression that are maintained throughout life by epigenetic mechanisms, which are described in
Chapter 5
, “The Dark Side Develops!”

Low social status is often characterized by violence, financial problems, poor health, shame and defeat, feelings of inferiority and
insecurity, and anxiety and depression. All of these are stressors, and drug use can be higher in this population. The importance of social status has been neatly demonstrated in well designed studies with animals. For example, Drs. M. Nader, D. Morgan, K. Grant, and others performed experiments showing that social rank in a group of monkeys can affect the dopamine system in the brain, and consequently, the amount of cocaine that is self-administered. In one study, monkeys (20 cynomologus macaques) were housed individually for one and a half years, and their D2 dopamine receptor levels were measured by PET scans. D2 dopamine receptors, critical parts of the dopamine system, were measured because they have been associated with addictive behavior as described in
Chapter 4
, “The ABCs of Drug Action in the Brain,” and
Chapter 7
, “The Brain Is Changed—For a Long Time!” Critical parts of their dopamine systems, the receptors, were measured when they were housed alone. Then, the animals were formed into five groups of four animals each, and the animals in each social group lived together for several months. During that time, the animals in the groups formed social hierarchies; dominant and subordinate monkeys emerged, as expected. The dominant monkeys were groomed more often by the others, were more aggressive, and were submitted to more often than the others. Their D2 receptor levels were again measured by PET scans, and their cocaine self-administration behavior was also measured.

The results were remarkable! The levels of D2 dopamine receptors increased in the brains of the animals that became dominant, but were unchanged in the subordinate animals! There was a relationship between social status and D2 dopamine receptor levels, and when the levels were found to be higher, the social status was higher (see
Table 9-1
). Because of the earlier discussion (in
Chapter 7
) that low D2 levels relate to greater drug taking, the drug intake of dominant animals was examined and compared to that of the subordinate animals. Low and behold, the dominant animals, the ones with the higher D2 receptor levels, took less cocaine than the subordinate animals.

Table 9–1 Effect of Changing from Individual to Social Housing, and the Effect of Establishing a Social Hierarchy

Placing the previously isolated animals in a social situation, where some become dominant, changed the biochemistry of the brains of the dominant ones and made them less vulnerable to cocaine, in just several months. Our social situations, or social rank if you will, can influence our brains and our vulnerability to take drugs, and presumably our vulnerability to other problems as well. This has many implications and questions for our lives. What is it in our brains, personality, or environment that determines our drive for dominance (or submission), and how does this impact our brain so that crucial changes occur in the brain? We can attempt a reasonable answer for the second question. Sensory input, like stress, activates the neurotransmitter systems in the brain, and, as described in
Chapter 4
, activation of neurotransmitter pathways can produce alterations (or plasticities) in these pathways. One kind of alteration is a change in levels of receptors or other components of the neurotransmission process.

We all experience what could be called “social defeats” in our lives. They might include being turned down when you ask someone to dance, being ridiculed publicly, or being excluded from a social group that is important to you. Moreover, you can become sensitized to it such that you feel defeated more easily when repeatedly confronted by the same defeating situation. Depending on exactly what the defeat is and depending on your social situation, needs, maturity, and resilience, you might be significantly affected by it. However, everyone has experienced situations of social defeat that can be quite devastating, and it is understandable that some turn to drugs to deal with the emotional pain. This has been studied in animals. For example, placing two male rats together under certain conditions results in one animal becoming subordinate or defeated. He might lie on his back and defer to the more dominant animal. In general, socially defeated animals behave differently. They explore less and are less active, they forage and eat less, and they engage in reproductive behavior less often. And here is the interesting part. The defeated animals also take some drugs such as cocaine more readily. Specifically, some experiments show that defeated animals learn to take cocaine faster than nondefeated animals.
³
A possible interpretation of this is that defeated animals (and humans too) are in pain and want drugs more. Social defeat, whatever that means for each of us, can promote drug use.

Stressful environments increase the vulnerability to use drugs. But what about pleasant or enriching environments? Do they do the opposite? There
is
strong evidence that they, in fact, will do the opposite.

Normally, laboratory rodents like mice or rats are housed under what are called standard conditions, which are adequately sized cages with bedding, food, and water. Enriched environments include larger cages with running wheels, small houses, and four or five colorful toys
of various shapes that are changed weekly. Animals stay in these enriched environments for perhaps 30 days before testing, and their behavior is compared to animals that stayed in standard housing.

Many laboratories have reported that environmental enrichment reduces cocaine seeking and stress-induced drug taking. In animals already experienced with cocaine (they have learned to self-administer it), environmental enrichment can reduce or even eliminate some addiction-related behaviors. Similar results have been found with other drugs such as heroin. When gene expression was examined in enriched animals (without drugs), many changes were found. Genes for proteins involved in synaptic transmission, protein production, cell structure, and metabolism were affected. These changes in the brain undoubtedly underlie the behavioral changes brought about by environmental enrichment. This work suggests that positive life conditions can change your brain chemistry and can even help addicts stay away from drugs. It is further suggested that positive environments can improve our lives in many, perhaps unexpected, ways. The important message here is that, like drugs, environments and behaviors change the brain. Because of this, they have the potential to serve as antidotes for drug addiction.

Stress in our lives is unavoidable, and dealing with it remains a problem for many people. We read self-help books, meditate, join various kinds of anti-stress groups and practices, complain, and suffer its effects. It might drive us to eat more for comfort, withdraw socially, or seek help from counselors. Even relatively common stressors such as overbearing bosses, traffic congestion, and so on, can promote drug taking. There is also early life stress that seems to predispose us to drug taking when we are adults, many months and years after the original stressor. Social rank and social defeat can also drive drug use. Thus, the effects of stressors are substantial and enduring, and stress
is clearly a risk factor for drug use and relapse to drug use. Fortunately, this risk factor can, at least to some degree, be controlled. Improved, positive environments seem to reduce vulnerability to drug seeking and relapse. Stress is something we need to learn to handle to reduce destructive consequences.

¹
Taken from
NIDA Notes
, Vol 14, April 1999.

²
The National Institute on Drug Abuse has made a special point about the importance of stress in addiction. See
NIDA Notes
, “NIDA Community Drug Alert Bulletin—Stress & Substance Abuse,” February 2006.

³
For example, see Tidey J.W., Miczek K.A. “Acquisition of cocaine self-administration after social stress: role of accumbens dopamine.”
Psychopharmacology (Berl)
, Apr;130(3):203-12, 1997.

As he drove past the casino, he could see the marquee, the valet parking stand...and the feelings started up again. He felt the thrill of placing a bet, of winning a pot. He felt energy, and his mind went faster. He wanted to be there, and he could feel the very cards in his hands...As he drove farther and the casino was left far behind, he mumbled, “Staying away is getting a little easier, but it’s far from easy.”

Can we be addicted to something besides drugs? Maybe we can. Consider the broad definition of addiction, which is a search for, or a preoccupation with something, that ends up being distressing or destructive to you, and you can’t easily stop.
¹
In recent years, there have been more and more studies of various forms of behavioral addiction such as excessive gambling, eating, and sexual activity. The different kinds of addictions have many things in common. First of all, the behavior takes up a lot of time and effort, and it gradually gets out of control such that attempts at stopping or controlling it are unsuccessful. These activities might result in conflicts with teachers, friends, and family members. It might affect the mood and health of the person, and impact the individual’s finances, education, or work. Sound familiar?

Excessive or pathological gambling can be considered as “addictive” in several ways. There are powerful rewards—money and the thrill of winning. The problem is that you need time and money to gamble, and this can obviously be a problem when a gambler is overextended and losing. It is sometimes regarded as an impulse
control problem. Many people stay away from gambling, saying that they don’t trust themselves. Like drug use, pathological gambling has been with us throughout history (see “
Gambling Addiction Is Ancient and Enduring
”), and it is not a passing fad. When a behavior is found over many generations and in many cultures, it seems that it is part of our human inclinations.

There have been many studies on gambling.
²
Studies of twins suggest that there is a genetic factor in becoming a gambler. If one member of a twin pair is a gambler, the other member is more likely to be a gambler than an unrelated person. Also, the dopamine system has been associated with gambling. Just as we have described a dysfunction of the frontal cortex in drug users, a similar problem has been found in gamblers who were studied using a card game. Gambling has been correlated with drug use suggesting a common connection or vulnerability of the two. Several imaging studies have shown that pathological gambling involves the same areas of the brain as substance abuse (for example, see
Figure 10-1
). This further implies that both gambling and substance abuse use the same neuronal circuits, such as the dopamine-containing mesolimbic circuit, which is so critical in drug abuse.

Figure 10-1. Gambling activates the same brain regions as drugs. Subjects participating in the study watched a game where they could either win or lose money. Activations (small darkened areas) were found in the Nucleus accumbens (near arrow tips), a region involved in drug abuse. The two images are at slightly different levels where the one on the right is more forward (towards the forehead). (Reprinted from Neuron, 30, Hans C. Breiter, Itzhak Aharon, Daniel Kahneman, Anders Dale, and Peter Shizgal, Functional Imaging of Neural Responses to Expectancy and Experience of Monetary Gains and Losses, 619-639, Copyright [2001], with permission from Elsevier.)