Dopamine and Depression by J.E.

Major Depressive Disorder is a disorder where individuals experience a number of symptoms including deep feeling of sadness and loss of pleasure or interest in previously enjoyed activities, as well as potentially sleep and appetite changes, problems with concentration and motivation, and feelings that life may not be worth living. It is a very complex and can be a chronic illness.

Networks in the brain

Brain cells are connected in large networks. There are places where two cells come into close contact and messages can be passed from one cell to the other (these places are called synapses). This happens by one of the cells releasing a chemical messenger (called a neurotransmitter) that can cross the short gap to the next brain cell and activate or inhibit it. There are lots of different neurotransmitters in the brain. How well they work plays a key role in a number of mental illnesses. There are three major neurotransmitters studied in depression: Dopamine, Serotonin and Noradrenaline.


Dopaminergic activity is complex and is regulated by multiple brain structures such as the hippocampus and the amygdala. Dopamine is produced in a part of the brain called the substantia nigra and the ventral tegmental area of the midbrain. These regions of the brain have many dopamine producing neurones and are linked with feelings of pleasure and the reward system in the brain.

The reward system

Research has shown that there is a relationship between the reward learning system of our brain and depression. In a non-depressed person positive or rewarding stimuli activate a part of the brain where dopamine receptors thrive and dopamine is released. Dopamine is responsible for allowing you to feel pleasure, satisfaction and motivation. When you feel good that you have achieved something, it's because you have a surge of dopamine in the brain. However, typically in a depressed person there is impaired responses to these positive or rewarding stimuli as a result of a reduction in dopamine released. Dopamine has 5 subtypes of receptors called D1, D2, D3, D4 and D5. These are being constantly produced and expressed in various cells in the body. It is not just the brain that requires dopamine to function. It can be classified as a “multifunctional” neurotransmitter getting us to think and to function in everyday life.

Dopamine influences our personality in a variety of ways. These include desire, motivation, goal setting and satisfaction.

STRESS induces changes in the level of dopamine. Dopamine release or dopamine metabolism is changed in response to stressful stimuli. Dopamine release can be enhanced or inhibited on the basis of the duration, intensity and the avoidability of the stressor [1].

Depression not only affects one’s mood and affect, but also daily functioning, cognition, and motivation with the aspect of impaired reward learning playing a role in the manifestation of its symptoms. Dysfunction of reward processing pathways are shown in depressed individuals.

Stress is a crucial factor in the development of depression [1]. In the general population only a subset of individuals display depression or anxiety; the others are said to be resilient. In lab rats exposed to stress, differences in the activity of neurones that release dopamine were studied and showed a difference between resilient and susceptible individuals.

Dopamine is involved in motivation, rewards, and pleasure. Dysfunction of the pleasure pathway is termed ANHEDONIA. Anhedonia is defined by the American Psychiatric Association 2013 as “A diminished interest or pleasure in response to stimuli that were previously perceived as rewarding before the development of the disorder”. Dopamine is involved in pleasure signalling in the pleasure pathway in the brain. Major Depressive Disorder includes anhedonia. It encompasses the complex reward related deficits such as disruption of anticipation, motivation and decision making, and processes involved in obtaining some type of reward [4]. Dysfunctions of the reward system, particularly the dopaminergic system is linked to anhedonia [2] .

Dopamine plays a role in reward prediction, motivational arousal and responses to incentive stimuli. It disrupts the motivation of depressed patients to seek out pleasurable experiences [2].

Medications and dopamine

Some patients on selective serotonin reuptake inhibitors (SSRIs) do not obtain remission from their depression. This might be due to the lack of effect of these medication on dopamine neurones. Some other types of antidepressants may have more effect on dopamine, such as bupropion (also used to help stop smoking) or higher doses of venlafaxine. It is also possible to augment (increase the action of) the antidepressant with a number of medications that may increase the number of dopamine spontaneously active neurones. Some antipsychotics, such as aripiprazole can do this. Other medications used for other conditions may also be helpful such as modafinil (used for a severe sleep disorder called narcolepsy) or pramipexole (used to help Parkinson’s Disease) can be used to augment an antidepressant.

Dopamine and Dopamine Transmission

Dopamine regulates reward-related behaviour through the mesolimbic dopaminergic pathway. The mesolimbic dopaminergic system is known as a major reward-related centre in the brain [1]. Changes in dopaminergic neurotransmission can alter responses to environmental stimuli involved in reward anticipation.

Exploring variation between short- and long-term depressive periods of study in subjects in relation to imaging evidence that the dopamine activity is not working as it should be, could offer an insight into the causality role of the brains reward circuit. Knowing there is a reduced dopaminergic transmission in the brain- could dopamine agonists (these bind to and activate dopamine receptors) be part of future pharmacological treatment of depression? Maintenance of stable and consistent dopamine activity may contribute to a cumulative long-term state of wellbeing and positive health.

Symptoms that may indicate less than optimal dopamine function

  1. Too much sleep and difficulty getting up on a morning
  2. Lack of ability to feel pleasure from things that normally interest you
  3. Lack of motivation
  4. Depression
  5. More introverted than usual
  6. Lack of mental energy ie concentration
  7. Weight Gain
  8. Addictive personality- addictive behaviour can sometimes be viewed as your brain’s attempt to get more dopamine
  9. Reduced sex drive


The brain reward system (BRS) are “neural pathways involved in eliciting rewarding experiences”[3].Dysfunction of the BRS function may be an underlying brain mechanism in the loss of pleasure/interest( anhedonic features) seen in major depressive disorder (MDD). BRS mediate reward behaviour e.g. pleasure and motivation. Rewards are biological or cognitive stimuli that are crucial in shaping our behaviour. The BRS pathways are extensive. There are neuroanatomical and neuropharmacological overlaps between MDD and the BRS. It is important to study the BRS when looking at the pathophysiology of depression.

Click here for references