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March 21, 2013

Combatting Chronic Stress and Fatigue Part 1 - Dopamine and Prolactin

HerbalEnergyBlogIngThough fatigue is among the most common health complaints patients report to their physicians, the condition is almost never addressed as a serious health problem in and of itself.  If the fatigue can’t be attributed to another disorder, the patient is usually given the safe, but more often than not, ineffective recommendations to simply get more sleep, and to try and eat a healthy diet.

Often times, the fatigued person is then left on his or her own to navigate a seemingly endless array of “solutions” which could include such things as energy and coffee drinks, stimulant pills, decongestants, “pre-workout” mixtures, soft drinks, or nicotine-containing tobacco products. 

The safety and biological soundness of such stimulants, however, simply can’t be assessed in the short term.  In other words, while most people judge stimulants merely by how they feel when they take them, this doesn’t provide any meaningful perspective on how the substance exerts its effects, or whether it constitutes a long-term solution.  Some of the most powerful stimulants often lose their effectiveness rapidly, and worse yet, many could have significantly negative side effects with continued use.

But, on the other hand, we mustn’t fall into the trap of damning all stimulants outright as many natural health advocates sometimes do.  There’s compelling research showing that some stimulants and energy-enhancing compounds may actually improve overall health. 

Where so many of us are seeking sustainable long-term solutions for fatigue, it’s prudent to gain a better understanding of which energy-enhancing substances can also impart long-term health benefits, and which substances are best avoided.

Dopamine – A Key to Enhancing Mood, Supporting Weight Loss, and Improving Overall Health

In beginning to investigate which psycho-stimulants may actually offer health benefits, one’s attention is naturally drawn to the effects of the neurochemical, dopamine.

At ideal levels, dopamine is an important contributor to positive mood, focus, drive, and goal-directed behavior.  With adequate dopamine, we feel confident and alert, our decision making is healthy, and we’re content in the knowledge that we possess the power necessary to shape our world.

In our modern age, however, it’s common for chronic stress to greatly compromise our dopamine levels. Under the influence of sustained stress, which inhibits dopamine production, we may notice that we’re more easily fatigued and chronically tired.  Our sex drive and libido suffer, and activities which we once enjoyed may lose their appeal.  As our motivation and drive erode, we often find it a constant struggle to maintain any meaningful level of ambition.  Our social relationships may suffer as we become increasingly more despondent and withdrawn.  Ultimately, the effect of low dopamine is usually a particularly stubborn sense of fatigue, depression, and despair. 

Worse yet, chronically-low dopamine levels (or low dopamine signaling / receptor sensitivity) may cause us to gravitate towards substances and behaviors which can give us an immediate (though temporary) dopamine fix.  It’s especially interesting to note the association between low dopamine levels and addiction.  The “hedonistic” pleasures of life – food, recreational drugs, smoking, sex, gambling – all serve to give us a potent dopamine surge.  It seems that the psychological torment of low dopamine is often so unbearable, that we’ll do just about anything to counteract it – even if the behaviors are ultimately unhealthy or life threatening.

Dopamine, Chronic Stress, Learned Helplessness, and Depression

For decades, psychologists have noted that animals and humans subjected to chronic and inescapable stress eventually lose the motivation and drive to escape these conditions – even when the stress becomes no longer inescapable.  This phenomenon is called learned helplessness, and researchers have found that the condition offers a powerful insight into common mood disorders.  At the stage where animals and humans largely give up on avoiding their adverse conditions, their symptoms manifest as those remarkably similar to chronic clinical depression.

Landmark studies in the field clearly illustrate this concept.  The first of many studies on learned helplessness involved three groups of dogs.  Those in the first group were restrained in harnesses, but quickly released.  Dogs in the second group were restrained in harnesses and subsequently given electric shocks, which they could stop by pressing a lever (i.e., they had some control over their adverse environment).  Dogs in the third group were restrained in harnesses, and given electric shocks at random which they could not stop – i.e., the stress was inescapable.  While the dogs in the first two groups rapidly recovered with no ill effects, the dogs in the third group developed symptoms concomitant with clinical depression.

In the second part of the study, the same three groups of dogs were tested in an apparatus where they could easily escape an electric shock by jumping over a low partition.  While dogs from the first two groups did so, dogs from the third group lay down passively and accepted the electric shocks – though escape was physically as easy for them as it was for the other groups, these dogs had lost the will to even attempt to free themselves from their torment.

Subsequent research has confirmed and strengthened these initial findings, and interestingly, in humans, the effect may even be more pronounced.  Studies have found that humans are capable of “vicarious learning” through which people can learn to be helpless merely through observing others undergoing stressful and inescapable events.

Our fast-paced modern world, of course, offers no shortage of chronically stressful situations.  It’s been noted that today, we generally work longer hours for less real pay than previous generations did, and it’s easy imagine why so many people feel trapped and powerless in a system which offers fewer and fewer rewards for their expended effort.  In the realm of physical fitness, failure to stick with diet and exercise plans is well known to be the norm rather than the exception.  Such chronic and repeated failure can induce a sort of learned helplessness wherein a person gives up due to the feeling that their fitness goals are simply impossible to achieve.

Dopamine – The Drive Chemical

Studies investigating the hormonal and neurochemical aspects of learned helplessness have begun to offer some insight into the condition – especially as relates to the yin-and-yang relationship of the “drive” chemical dopamine, and its antagonist, the pituitary stress hormone, prolactin.

Primate studies have found that African green monkeys held in captivity experienced elevated cortisol levels (an acute stress hormone) for two days after capture, but while their cortisol levels eventually normalized, their levels of prolactin elevated steadily as their time in captivity increased:  

Study Link - Physiologic manifestations of stress from capture and restraint of free-ranging male African green monkeys (Cercopithecus aethiops).

Quote from the above study:

Mean prolactin concentration was significantly lower in the wild-caught monkeys on day 2 after capture, and the levels increased gradually to 45 days in captivity and was highest in monkeys that had been captive for 7 mo.

As such, prolactin could be seen as acting as a long-term stress hormone under prolonged periods of inescapable stress.  It’s not likely a coincidence that the symptoms of prolactin excess are exactly those which sap our drive, motivation, and zest for life:

Symptoms of Prolactin Excess:

Mood Changes / Depression Decreased Motivation
Low Libido / Impotence Hostility / Anxiety
Decreased Testosterone Infertility
Fatigue Lack of Drive

In biological circles at least, it’s well known that the chemical most responsible for keeping prolactin in check is dopamine.  In fact, dopamine is sometimes referred to by the alternate names, prolactin-inhibiting factor (PIF), prolactin-inhibiting hormone (PIH), or prolactostatin.  It’s no coincidence either, that the symptoms of low dopamine almost exactly mirror the symptoms of elevated prolactin.

Signs of Low Dopamine:

Inability to Love Lack of Ambition
Low Libido Withdrawal
Erectile Dysfunction Low Energy / Fatigue
Addictions Social Anxiety
Depression Lack of Remorse
Anhedonia — the inability to experience pleasure.  

Whereas healthy dopamine levels are associated with the opposite:

Signs of Healthy Dopamine Levels:

Feelings of well-being Sound Decision Making
Healthy Libido Realistic Expectations
Healthy Bonding Good Feelings Toward Others
Pleasure in Accomplishing Tasks Motivation
Energy and Vitality  


Prolactin and Cancer

The tandem of low dopamine and high prolactin levels likely affects not just our moods – but every aspect of our health.  In fact, prolactin and dopamine are two stress-related chemicals that may play a major role in helping to explain the association between chronic stress and somatic (bodily) diseases.  Prolactin, for example, has been found to play a role in stimulating the growth of hormone-sensitive cancers of the breast and prostate:

Study Link - Prolactin in breast and prostate cancer: molecular and genetic perspectives.

Conversely, dopamine has been shown to counter many of the effects of prolactin in breast and prostate cancer cells, and has been proposed as a potential therapeutic agent in the disorders:

Study Link - Dopamine stabilizes tumor blood vessels by up-regulating angiopoietin 1 expression in pericytes and Krüppel-like factor-2 expression in tumor endothelial cells.

Quote from the above study:

There is increasing evidence for a role of dopamine in the development of obesity. More specifically, dopaminergic hypofunction might lead to (over)compensatory food intake.

Low Dopamine / High Prolactin and Weight Gain

Similarly, excesses of prolactin are known to cause weight gain as well.  Classes of medications which increase prolactin levels (many by specifically antagonizing dopamine) are notorious for causing weight gain:

Study link - Body weight gain induced by antipsychotic drugs: mechanisms and management.

Quote from the above study:

…when [sulpiride] was administered to healthy men their weight gain was significant, and prolactin was found to be the only variable that correlated positively with the [body weight gain].

The weight gain which often accompanies smoking cessation may have more to do with dopamine than with mere changes in metabolic rate.  It seems that the dopamine fix afforded by nicotine is often replaced with the dopamine fix afforded by overeating.  It’s likely no coincidence, therefore, that the most successful medication for assisting smoking cessation without weight gain acts upon the dopaminergic system:

Study Link - Smoking cessation and weight gain.

… body weight gain at the end of treatment was significantly lower in the patients receiving bupropion or bupropion plus nicotine patch, compared with placebo.

Ultimately, the balance of dopamine and prolactin play a role throughout every aspect of our health including energy levels and fatigue, mood disorders, weight gain (and associated sequelae), neurodegenerative disease, bone loss, and cancer.

Knowing this, it seems prudent to investigate, not just ways to keep ourselves alert, but, at the same time, ways to mitigate the effects of chronic stress by supporting healthy dopamine metabolism.

In subsequent articles, we’ll examine ways to foster healthy dopamine levels and proper dopamine signaling using certain “stimulants,” adaptogens, and activities. 

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