| RESEARCHED AND WRITTEN BY Zofia Hochtaubel
| EDITED BY Yushu Lin
There are over 100 neurotransmitters in our brain—the molecules the nervous system uses to transmit messages between neurons or from neurons to muscles. These chemicals' interactions play a key role in our lives by controlling our bodies. One of them is particularly interesting.
4-(2-aminoethyl)benzene-1,2-diol, or to put it simply, dopamine, is an organic compound belonging to the group of catecholamines, a component of a wide group of neurotransmitters called biogenic amines. Due to the presence of an amino group (-NH2), it can also be classified as a base; therefore, it has excellent solubility in water. Thanks to this feature, in the event of a dopamine deficiency, it can be administered via a drip.
Dopamine is synthesized in the neurons of the midbrain, more precisely in its substantia nigra, and is primarily responsible for proper muscle function and motor coordination; controlling human metabolism, and maintaining normal blood pressure. In the psyche, it is responsible for finding one's way in reality and supports concentration and memory. Thanks to dopamine, a person is able to think abstractly, set new goals, and plan long-term.
But how exactly does it work? How does a small organic compound influence our lives? To answer these questions we have to understand how dopamine pathways work.
Dopaminergic neurons are groups of nerve cells that synthesize, store, and release dopamine. They are relatively few; it is estimated that there are about 400,000 in a human's brain. Dopaminergic neurons form four dopamine pathways: tuberoinfundibular, nigrostriatal, mesolimbic, and mesocortical.
The nigrostriatal pathway's dopaminergic nuclei are located in locus niger, from which axons travel to the vertebral part of the strip. The main function of the nigrostriatal pathway is to influence voluntary movement through basal ganglia motor loops. Movement is influenced through the direct and indirect pathways of movement. The direct pathway promotes desired movement by synapsing dopamine D1 receptors, resulting in an excitatory effect on the thalamus and motor cortex.
On the contrary, the indirect pathway, which involves projections from dopamine D2 receptors, has an overall net inhibitory effect on thalamic and motor cortex movement. Degeneration of dopaminergic fibers is one of the features of Parkinson's disease. Decreased dopamine levels can also cause tremors, acinesia (motor impairment), postural imbalance, or bradycardia.
The nigrostriatal dopamine pathway, along with the mesolimbic and mesocortical dopaminergic pathways, can also influence other brain functions, including cognition, reward, and addiction.
The mesolimbic pathway and mesocortical pathways form the backbone of the reward system, which is responsible for regulating behaviors and reactions such as motivation, pleasure, or discomfort. Dopaminergic nuclei of the mesolimbic pathway are located in the ventral tegmental area, from where they send axons to the nucleus accumbens. The mesolimbic pathway is part of the limbic system, and its dopaminergic projections primarily regulate motivational and emotional activities (pleasure and euphoria, but also delusions or obsessions). Increased dopaminergic transmission is associated with the development of symptoms of psychosis (often occurring in schizophrenia). It is important to note that the receptors of the neurons that make up the mesolimbic pathway are the final point of action for many psychoactive substances.
The mesocortical pathway also sends its projections from the ventral tegmental area; however, their axons have their endings in the prefrontal cortex. The dopaminergic projections of this pathway regulate the processes of learning, memorization, and motivation. However, the role of dopamine in motivation is not limited to providing a sense of pleasure and reward. It stimulates the desire to undertake activities aimed at achieving something positive and avoiding negative stimuli. The results of clinical trials also show that the levels of dopamine in individual people are different, which in turn translates into different degrees of perseverance in the pursuit of the goal. A reduced level of dopamine eliminates the desire to take any action, which can turn a person into a couch potato. Conversely, an increased level of this neurotransmitter can result in a tendency to risk behavior. In terms of learning, the decreased dopaminergic transmission of the mesocortical pathway is manifested by cognitive disorders.
Dopaminergic neurons present in the frontal lobe are also involved in concentration processes. Since dopamine is an important neurotransmitter regulating the reward system, its proper activity also allows us to focus on the most important tasks. Dopamine deficiency leads to a decrease in concentration levels. Scientists believe that when this situation persists in the body for a long time, it may lead to the development of ADHD.
The last but not least of the dopaminergic pathways is the tuberoinfundibular tract, which is responsible for hormonal management. The dopaminergic nuclei of this pathway are located in the hypothalamus and send their projections to the anterior part of the pituitary gland, where they regulate the secretion of prolactin into the bloodstream. Prolactin is a hormone that stimulates the mammary glands to produce milk.
Dopamine is an inhibitor of prolactin secretion. Decreasing dopamine levels or blocking of dopamine receptors by dopamine antagonists can cause an uncontrolled increase in prolactin levels in the body. This, in turn, can contribute to, among other things, lactation disorders or problems with pregnancy in women. In men, high levels of prolactin can result in gynecomastia.
Dopamine plays a great role in our brain. Even small changes in its levels influence our behavior. However, there are still so many questions left without an answer, especially in terms of dopamine's association with neurological diseases. Nevertheless, scientists work hard to provide as many answers as they can and use their knowledge to improve the treatment of Parkinson's disease, schizophrenia, and ADHD.
Sources:
"Dopamine: Functions, Signaling, and Association with Neurological Diseases" by Marianne O Klein, Daniella S Battagello, Ariel R Cardoso, David N Hauser, Jackson C Bittencourt, Ricardo G Correa
"The neurobiology of dopamine signaling" by Jean-Antoine Girault, Paul Greengard
"What does dopamine mean?" by Josh Berke
"Dopamine Modulation of Motor and Sensory Cortical Plasticity among Vertebrates" by Matheus Macedo-Lima and Luke Remage-Healey
"Dopamine receptors and brain function" by Mohamed Jaber, Susan W Robinson, Cristina Missale, Marc G Caron
"Dopamine in motivational control: rewarding, aversive, and alerting" by Ethan S. Bromberg-Martin, Masayuki Matsumoto, and Okihide Hikosaka
"Dopamine in schizophrenia: a review and reconceptualization" by K L Davis, R S Kahn, G Ko, M Davidson
"The Role of Dopamine in Schizophrenia from a Neurobiological and Evolutionary Perspective: Old Fashioned, but Still in Vogue" by Ralf Brisch, Arthur Saniotis, Rainer Wolf, Hendrik Bielau, Hans-Gert Bernstein, Johann Steiner, Bernhard Bogerts, Katharina Braun, Zbigniew Jankowski, Jaliya Kumaratilake, Maciej Henneberg, and Tomasz Gos
"Attention-deficit-hyperactivity disorder and reward deficiency syndrome" by Kenneth Blum, Amanda Lih-Chuan Chen, Eric R Braverman, David E Comings, Thomas JH Chen, Vanessa Arcuri, Seth H Blum, Bernard W Downs, Roger L Waite, Alison Notaro, Joel Lubar, Lonna Williams, Thomas J Prihoda, Tomas Palomo, and Marlene Oscar-Berma
"Dopamine and Levodopa Prodrugs for the Treatment of Parkinson’s Disease" by Fatma Haddad, Maryam Sawalha, Yahya Khawaja, Anas Najjar, and Rafik Karaman
Encyclopedia of Neurophysiology :
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