The Brain, Neurotransmitters, Dopamine, Serotonin and Happiness Medicine

Dopamine and serotonin are key happiness monoamine neurotransmitters. In this blog, i will examine the areas of the brain where the perception of happiness appears to be located (Section A). Thereafter, the dopamine and serotonin happiness neurotransmitters will be looked at. (Section B).

SECTION A

The Brain: the seat of happiness consciousness ?

The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. The brain is located in the head, usually close to the sensory organs for senses such as vision. The brain is the most complex organ in a vertebrate’s body. In a human, the cerebral cortex contains approximately 15–33 billion neurons, each connected by synapses to several thousand other neurons. These neurons communicate with one another by means of long protoplasmic fibers called axons, which carry trains of signal pulses called action potentials to distant parts of the brain or body targeting specific recipient cells. (1). For perception of happiness to occur, this structural framework needs to be functioning correctly.

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In this perspective, neuroscience studies confirm that different parts of the brain play a role in the expression of happiness, in particular the prefrontal cortex, (2) the amygdala, the hippocampus, the limbic system and the olfactory bulb.

“The emotion circuitry of the brain is complex, involving primarily structures in the prefrontal cortex, amygdala, hippocampus, anterior cingulated cortex, and insular cortex. These structures normally work together to process and generate emotional information and emotional behavior. Research has particularly focused on the prefrontal cortex which, unlike most other brain regions involved in emotion processing, shows asymmetric activation in relation to positive and negative emotions” (3).

The olfactory bulb is also at play with regarding to emotions, therein,  a special structure  processes olfactory sensory signals and sends its output to the olfactory part of the pallium. It is a major brain component in many vertebrates, including in humans, albeit reduced. (4)

Other “happiness” ares of the brain have been identified, albeit less known areas. Serotonin, for example (the primary target of antidepressant drugs and many dietary aids)  comes  from a small brainstem area called the Raphe nuclei. (5)  Norepinephrine, which is involved in arousal, comes  from a nearby small area called the locus coeruleus. Other neurotransmitters such as acetylcholine and dopamine have multiple sources in the brain, but are not as ubiquitously distributed as glutamate and GABA. (6)

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SECTION B

Neurotransmitters and synapses

Neurotransmitters are chemicals that are released at synapses when  they are activated. They can also be released by neurons (nerve cells) to send signals to other nerve cells. Neurotransmitters attach themselves to receptor molecules on the membrane of the synapse’s target cell, and thereby alter the electrical and chemical properties of the receptor molecules. With few exceptions, each neuron in the brain releases the same chemical neurotransmitter, or combination of neurotransmitters, at all the synaptic connections it makes with other neurons.  (7) In  this perspective, a neuron can be characterized by the neurotransmitters that it releases. (8)

The two neurotransmitters that are used most widely in the vertebrate brain are glutamate, which almost always exerts excitatory effects on target neurons, and gamma-aminobutyric acid (GABA), which is almost always inhibitory. Neurons using these transmitters can be found in nearly every part of the brain. (9)

There are dozens of other chemical neurotransmitters that are used in more limited areas of the brain, often areas dedicated to a particular function. This is where the happiness neurtransmitters come in.

The Central Happiness Neurotransmitters

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 Top: A dopamine molecule consists of a catechol structure (a benzene ring with two hydroxyl side groups) with one amine group attached via an ethyl chain. As such, dopamine is the simplest possible catecholamine, a family that also includes the neurotransmitters norepinephrine and epinephrine.

Dopamine

One of the most important neurotransmitters that modulates mood and wellbeing is dopamine. (10) Ashby et al have shown that positive mood is associated with (but not necessarily caused by) increased levels of dopamine in the brain and some of the changes in cognition observed in positive mood are due to the increased dopamine levels. (11) Most organisms studied to date utilize a reward–punishment mechanism (12). Other brain dopamine pathways are involved in motor control and in controlling the release of various hormones. These pathways and cell groups form a dopamine system which is neuromodulatory. (13)

Dopamine also promotes many pleasurable experiences (14) from food enjoyment, sexual activity to learning via the reward mechanism. (15)

Another important effect of dopamine is as a “teaching” signal. (16) When an action is followed by an increase in dopamine activity, the basal ganglia circuit is altered in a way that makes the same response easier to evoke when similar situations arise in the future. (17) This is a form of operant conditioning, in which dopamine plays the role of a reward signal. (18) Lastly, dopamine has an immune function, the regulation of which also affects wellbeing. (19)

 Serotonin

Another neurochemical agent that is associated with emotional states is serotonin (5HT). (20) Serotonin is a neurotransmitter that mediated satisfaction, happiness and optimism. Serotonin levels are reduced in depression, and most modern anti-depressant drugs, known as serotonin reuptake inhibitors (SSRIs), act by increasing the amount of serotonin available to brain cells. Researches indicated that increased of serotonin level was related to positive mood. (21)

Approximately 90% of the human body’s total serotonin is located in the enterochromaffin cells in the GI tract, where it is used to regulate intestinal movements. The remainder is synthesized in serotonergic neurons of the CNS, where it has various functions. These include the regulation of mood, appetite, and sleep. Serotonin also has some cognitive functions, including memory and learning.  (22)

In response to the perceived abundance or scarcity of resources, an animal’s growth, reproduction or mood may be elevated or lowered. This may somewhat depend on how much serotonin the organism has at its disposal. (23)

Thus, serotonin is involved not only in the perception of food availability but also in social rank. In macaques for example, alpha males have twice the level of serotonin released in the brain than subordinate males and females. (24)

Christian Joubert  CSO & HMI director

(In subsequent blogs,  we cover other neurotransmitters that impact welbeing).

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Reference and Precision Notes
(1). Pelvig, DP; Pakkenberg, H; Stark, AK; Pakkenberg, B (2008). “Neocortical glial cell numbers in human brains”. Neurobiology of Aging. 29 (11): 1754–1762
(2). Most of the enlargement of the primate brain comes from a massive expansion of the cerebral cortex, especially the prefrontal cortex and the parts of the cortex involved in vision. The visual processing network of primates includes at least 30 distinguishable brain areas, with a complex web of interconnections. It has been estimated that visual processing areas occupy more than half of the total surface of the primate neocortex. The prefrontal cortex carries out functions that include planning, working memory, motivation, attention, and executive control. It takes up a much larger proportion of the brain for primates than for other species, and an especially large fraction of the human brain. Cf. Sereno, MI; Dale, AM; Reppas, AM; Kwong, KK; Belliveau, JW; Brady, TJ; Rosen, BR; Tootell, RBH (1995). “Borders of multiple visual areas in human revealed by functional magnetic resonance imaging” (PDF). Science. AAAS. 268 (5212): 889–893.  And Fuster, JM (2008). The Prefrontal Cortex. Elsevier. pp. 1–7
(3) Huppert FA (2009). Psychological Well-being: Evidence Regarding its Causes and Consequences. Appl Psychol: Health and Well Being, 1 (2): 137–164.
(4). Humans and other primates have these senses reduced because they  are dominated by information acquired more by sight than smell. But the olfactory senses are still connected to the limbic system and modulates emotions, we see this with essential oils. Cf. Northcutt, RG (1981). “Evolution of the telencephalon in nonmammals”. Annual Review of Neuroscience. 4: 301–350.
(5). Frazer, A; Hensler, JG (1999). “Understanding the neuroanatomical organization of serotonergic cells in the brain provides insight into the functions of this neurotransmitter”. In Siegel, GJ. Basic Neurochemistry (Sixth ed.). Lippincott Williams & Wilkins
(6). Rang, HP (2003). Pharmacology. Churchill Livingstone. pp. 476–483. ISBN 0-443-07145-4.
(7). Kandel, Eric R.; Schwartz, James Harris; Jessell, Thomas M. (2000). Principles of neural science. New York: McGraw-Hill.
(8). The great majority of psychoactive drugs exert their effects by altering specific neurotransmitter systems. This applies to drugs such as cannabinoids, nicotine, heroin, cocaine, alcohol, fluoxetine, chlorpromazine, and many others. Cf. Cooper, JR; Bloom, FE; Roth, RH (2003). The Biochemical Basis of Neuropharmacology. Oxford University Press. Also, because of their ubiquity, drugs that act on glutamate or GABA tend to have broad and powerful effects. Some general anesthetics act by reducing the effects of glutamate; most tranquilizers exert their sedative effects by enhancing the effects of GABA.
(9).  McGeer, PL; McGeer, EG (1989). “Chapter 15, Amino acid neurotransmitters”. In G. Siegel; et al. Basic Neurochemistry. Raven Press. pp. 311–332.
(10). Dopamine (DA, contracted from 3,4-dihydroxyphenethylamine) is an organic chemical of the catecholamine and phenethylamine families that plays several important roles in the brain and body. It is an amine synthesized by removing a carboxyl group from a molecule of its precursor chemical L-DOPA, which is synthesized in the brain and kidneys. Dopamine is also synthesized in plants and most animals. In the brain, dopamine functions as a neurotransmitter—a chemical released by neurons (nerve cells) to send signals to other nerve cells. The brain includes several distinct dopamine pathways, one of which plays a major role in reward-motivated behavior. Most types of rewards increase the level of dopamine in the brain, and many addictive drugs increase dopamine neuronal activity.
(11). Ashby FG, Isen AM, Turken AU (1999). A neuropsychological theory of positive affect and its influence on cognition. Psychol Rev, 106: 529–550.
(12). For instance, in vertebrates, the reward-punishment system is implemented by a specific set of brain structures, at the heart of which lie the basal ganglia, a set of interconnected areas at the base of the forebrain. The basal ganglia are the central site at which decisions are made: the basal ganglia exert a sustained inhibitory control over most of the motor systems in the brain; when this inhibition is released, a motor system is permitted to execute the action it is programmed to carry out. Rewards and punishments function by altering the relationship between the inputs that the basal ganglia receive and the decision-signals that are emitted. The reward mechanism is better understood than the punishment mechanism, because its role in drug abuse has caused it to be studied very intensively. Research has shown that the neurotransmitter dopamine plays a central role: addictive drugs such as cocaine, amphetamine, and nicotine either cause dopamine levels to rise or cause the effects of dopamine inside the brain to be enhanced. Hyman, SE; Malenka, RC (2001). “Addiction and the brain: the neurobiology of compulsion and its persistence”. Nature Reviews Neuroscience. 2 (10): 695–703.
(13).  IUPHAR/BPS guide to pharmacology. International Union of Basic and Clinical Pharmacology.
(14) Wise RA (2008). “Dopamine and reward: the anhedonia hypothesis 30 years on”. Neurotox Res. 14 (2–3): 169–83.
(15 ) Arias-Carrión O, Pöppel E (2007). “Dopamine, learning and reward-seeking behavior”. Acta Neurobiol Exp. 67 (4): 481–488.
(16) Chakravarthy VS, Joseph D, Bapi RS (2010). “What do the basal ganglia do? A modeling perspective” (PDF). Biological Cybernetics. 103 (3): 237–53.
(17). All addictive drugs directly or indirectly affect dopamine neurotransmission in the nucleus accumbens. these drugs increase drug “wanting”, leading to compulsive drug use, when repeatedly taken in high doses. Drugs that increase synaptic dopamine concentrations include psychostimulants such as methamphetamine and cocaine. These produce increases in “wanting” behaviors, but do not greatly alter expressions of pleasure or change levels of satiation.
(18) Floresco SB (2015). “The nucleus accumbens: an interface between cognition, emotion, and action” (PDF). Annual Review of Psychology. 66: 25–52.
(19). In the immune system dopamine acts upon receptors present on immune cells, especially lymphocytes. Dopamine can also affect immune cells in the spleen, bone marrow, and circulatory system. In addition, dopamine can be synthesized and released by immune cells themselves. (Cf below, Buttarelli et al) The main effect of dopamine on lymphocytes is to reduce their activation level. The functional significance of this system is unclear, but it affords a possible route for interactions between the nervous system and immune system, and may be relevant to some autoimmune disorders. Cf. Buttarelli FR, Fanciulli A, Pellicano C, Pontieri FE (2011). “The dopaminergic system in peripheral blood lymphocytes: from physiology to pharmacology and potential applications to neuropsychiatric disorders”. Current Neuropharmacology. 9 (2): 278–88. See aso,  Sarkar C, Basu B, Chakroborty D, Dasgupta PS, Basu S (2010). “The immunoregulatory role of dopamine: an update”. Brain, Behavior, and Immunity. 24 (4): 525–8.
(20) Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract (GI tract), blood platelets, and the central nervous system (CNS) of animals, including humans. It is popularly thought to be a contributor to feelings of well-being and happiness.
(21). Mitchell RLC, Phillips LH (2007). The psychological, neurochemical and functional neuroanatomical mediators of the effects of positive and negative mood on executive functions. Neuropsychol, 45: 617–629.
(22).  King MW. “Serotonin”. The Medical Biochemistry Page. Indiana University School of Medicine.
Berger M, Gray JA, Roth BL; Gray; Roth (2009). “The expanded biology of serotonin”. Annu. Rev. Med. 60: 355–66. Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis, http://www.cell.com/cell/abstract/S0092-8674(15)00248-2
(23).  Coila, Bridgett. “Effects of Serotonin on the Body.” LiveStrong. n.p., 20 June. 2010. Web. 11 Aug. 2013
(24). As measured by the levels of 5-Hydroxyindoleacetic acid (5-HIAA) in the cerebro-spinal fluid). Dominance status and cerebro-serotonin levels appear to be positively correlated. When dominant males were removed from such groups, subordinate males begin competing for dominance. Once new dominance hierarchies were established, serotonin levels of the new dominant individuals also increased to double those in subordinate males and females. The reason why serotonin levels are only high in dominant males but not dominant females has not yet been established. Serotonin is evolutionary conserved and appears across the animal kingdom. It is seen in insect processes in roles similar to in the human central nervous system, such as memory, appetite, sleep, and behavior. Locust swarming is mediated by serotonin, by transforming social preference from aversion to a gregarious state that enables coherent groups. Learning in flies and honeybees is affected by the presence of serotonin. Cf. “Serotonin is critical for rewarded olfactory short-term memory in Drosophila.”. J Neurogenet. 26: 238–244. 2012
Disclaimer: Nothing in this pedagogical blog should be construed as medical advise.
2017 (c) Happiness Medicine Institute and agents. All rights reserved

Trained in Conventional Medicine, Traditional Chinese Acupuncture, Naturopathy, oenology and Law, Professor Joubert teaches in different parts of the world how to extend a healthy Lifespan to 120 years and beyond, Pr. Joubert is working on a Documentary and book that redefines Medicine in light of new discoveries, ancient wisdoms, innovative research and holistic science, but he can be nonetheless available to coach patients back to homeostasis, wellbeing & Joie de Vivre. On occasion, Pr Joubert can also coach health professionals to better protect their holistic practice when they must deviate from outdated and irrational “standards of care”. See links on “Contact” and “Mission” (under the “About” link) for details.

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