Sample Essay: The Role of Dopamine on the Brain

Dopamine is one of the three most studied monoamines of in the field of psychiatry along with norepinephrine and serotonin. It has a huge impact on brain activities in its role as a neurotransmitter.  Dopamine has a single amine (-NH2-) group as do norepinephrine and serotonin and it is further subcategorized as a catecholamine because of its molecular structure that includes a catechol group (Keltner et al, 2000). Dopamine is distributed in a concentrated manner in several discrete neural pathways as well as more diffusely in the brain.  These pathways are often linked to important regions in the brain that mediate important behaviors and there is theory and evidence that dopamine levels cause intense changes in behavior mainly due to their role as neurotransmitters in the brain. Dopamine pathways in the brain explain behavioral phenomena such as syntax production and probability reasoning to activation of specific motor programs and learning of motor programs. For example, Parkinson’s patients who have depleted levels of dopamine in the brain have problems with ordinary syntax and motor control (Schulkin, 2004). Thus, the role of dopamine in the brain is one that is worth study and investigation.

Neurotransmitters such as dopamine are chemical messengers released by neurons to surrounding regions in the brain to signal them to fire nerve impulses or initiate metabolic changes (Foltynie et al, 2003). The release of these neurotransmitters is carefully regulated by the body through receptors and transporters. Receptors are located on nerve cells and when they receive a neurotransmitter such as dopamine, they cause the neuron to fire a nerve impulse. Transporters which are present on the surface of the transmitting neuron help to bring back the neurotransmitters to the nerve cell so that it is ready for the next burst. The neurotransmitter dopamine is stored in tiny hollow spheres, called vesicles which are tiny buds on the nerve cell’s surface. When the nerve impulse travels and reaches the end of a nerve process, the transmitting neuron is triggered to release dopamine into the narrow space between neurons called the synapse (Foltynie et al, 2003). When the dopamine reaches the receiving neuron, it binds to specific dopamine receptors, thereby triggering a response in that neuron. Almost immediately, the dopamine transporter scavenges excess dopamine from the synapse to terminate the signal. However, in the absence of dopamine receptors dopamine will have no action.

There are five types of dopamine receptors –D1 to D5 and they are located at different places in the brain. D1 receptors are located in the cortex and in the extrapyramidal system; D2 receptors are located in limbic structures, motor centers, and the pituitary. D3 receptors are located in limbic areas. D4 receptors are located on cortical neurons that influence thought processes. D5 receptors are located in the limbic system, including the nucleus accumbens, which is a major component of the reward pathway (Keltner et al, 2001). By knowing the type of dopamine receptor it is possible to know its location and thereby understand various drug effects and discover new receptor specific drugs. For example, Bezchlibnyk-Butler and Jeffries (1997) have observed that blocking the D1 receptors may mediate the antipsychotic effects of neuroleptics while blocking D2 receptors controls positive symptoms, causes extrapyramidal symptoms, and causes prolactin elevation (Keltner et al, 2001, p. 65). Likewise, blockade of D3 receptors and D4 receptors can exacerbate the antipsychotic effect on negative symptoms and positive symptoms respectively; blockade of D5 receptors is predicted to create an antipleasure response.

As a result of such specific reactions to dopamine receptor stimulation and antagonism, there have been many scientific deductions. Studies show that the efficiency of traditional antipsychotics is highest when 70% to 80% of D2 receptors are blocked (Hertel, Fagerquist, & Svensson, 1999).  Agents that block D3 receptors can have an ameliorating effect on Type II schizophrenia due to its association with negative symptoms. The drug clozapine has a stronger attraction for D4 than D3 and hence there can be both positive and negative effects (Keltner et al, 2001).   Of all the dopamine receptor information, the D2 receptor information has been most applied in clinical settings. The other receptors have been found to play smaller roles in the treatment of schizophrenia (Keltner et al, 2001).

Generally, it has been found that dopamine receptor stimulation can cause “positive symptoms of schizophrenia, psychoses, Huntington’s disease, dyskinesias, hallucinations, delusions, nausea, vomiting, addictive behaviors and sexual function enhancement” whereas dopamine receptor antagonism can cause “negative symptoms of schizophrenia, temperature dysregulation, antiemetic effects, Parkinson’s and related disorders, dystonias, akathisias, cognitive problems, sexual dysfunction and neuroendocrine dysregulation” (Keltner et al, 2001, p. 68). Dopamine receptors are targets of drug therapy for schizophrenia and other dopamine-related disorders. The original biochemical model of schizophrenia was called the dopamine hypothesis, and for many years drug treatment was aimed at antagonizing these receptors. Both this theory and antischizophrenic medications have been modified over the years. In people with Parkinson’s disease, dopamine-producing neurons in the substantia nigra start to die off, and the brain gradually loses control of physical movements. Tremors and eventually paralysis result (Keltner et al, 2001).

Dopamine is concentrated in four brain systems or pathways, where the cell bodies are in one location and long fibers extend from these locations to terminate elsewhere in the brain. The nigrostriatal dopamine tract is the most studied of the brain’s dopamine systems (Heinrichs, 2001). It rises from the sustantia nigra and stretches to the neostriatus, which is part of the basal ganglia. The basal ganglia region is responsible for the modulation of movement and action and the learning of motor skills and procedures. Disorders like Parkinsonism deplete the tract’s dopamine and result in rapid shaking or resting tremor that recedes with voluntary movement (Heinrichs, 2001). Moreover, patients show muscular rigidity, an inflexible expressionless face and general slowing of motor activity that affects walking and speaking. Treatment of Parkinsonism has focused on increasing dopamine activity in the brain. Though Dopamine  is present in the blood supply, it is prevented from entering the brain by the blood brain barrier – a network of cells that transport nutrients to neurons but filter out certain substances (Heinrichs, 2001). However dihydrozyphylalanine of DOPA, the immediate precursor of dopamine has the ability to enter the brain from the bloodstream and therefore it is used in treating Parkinson’s disease.

A second major dopamine tract in the brain is the mesolimbic pathway which rises up from the ventrotegmental area of the midbrain to the nucleus accumbens, septum, amygdala and entorhinal cortex and these areas have been associated with reward, fear, anxiety and some aspects of memory. A third pathway is the mesocortical tract that rises to the prefrontal cortex that is associated with activities such as planning and self regulation (Heinrichs, 2001). A final pathway occurs in the hypothalamus and extends to the pituitary gland. The effect of blocking dopamine activity in this system can be seen to interfere with the activity of the pituitary and cause weight gain, lower sex drive and excessive prolactin release (Heinrichs, 2001).

It has been found that a gene called Sry that is found on the Y chromosome and hence exclusively found in men – is the key to dopamine regulation in the brain (Gramling, 2006). This finding explains why men are more often likely to suffer from dopamine-related illnesses such as Parkinson’s disease, schizophrenia, and addiction. Together with another new study, the work suggests that women and men have distinctive dopamine-regulating systems. Men are 1.5 times as likely as women to develop Parkinson’s disease (Gramling, 2006). A recent study on dopamine neurons in the brains of macaques has shows that this dopamine can predict rewarding events as one of its functions in specific regions of the brain (Schulkin, 2004). Once prediction is made, the dopamine neurons tend to fire more in anticipation of rewarding events. In this experiment involving macaques, before a reward is fully predictable, dopamine neurons are activated each time the reward is given. However one the reward is predictable, dopamine is no longer activated to the same degree. And if the predicted award does not happen, dopamine release is again activated – the greater the uncertainty of reward occurrence the greater activation of the dopamine neuronal population (Schulkin, 2004). This is a model of expectancy and learning and the model of dopamine release should have some application to aesthetic appreciation and perception of beauty. Thus, dopamine is a neurotransmitter that serves the dual purpose of organizing movement and organizing thought by the prediction of events (Schulkin, 2004).  Moreover, it has been found that dopamine expression is essential for incentive motivation – it provides the list of objects to approach and list of objects to avoid.  As dopamine is released whenever rewarding acts are performed such as eating, shopping, sex, etc, there is a sense of pleasure and this feeling of pleasure can lead to an addiction in some cases (The Mail on Sunday, 2008). According to a very recent study, in the case of patients with fibromyalgia, changes in the levels of dopamine can cause lowering of gray matter density in areas of the brain where dopamine is known to control neurological activity (Forbes.com, 2009). The dopamine system does not function in isolation. Rather, it functions along with a number of other neurotransmitters and neuropeptides in a variety of locations in the brain.

Bibliography:

Bezchlibnyk-Butler, K. Z. & Jeffries, J. J. (1997). Clinical handbook of psychotropic drugs. Hogrefe & Huber, Seattle

Foltynie, Thomas; Lewis, Simon and Barker, A. Roger (2003). Parkinson’s Disease: Your Questions Answered. Elsevier Health Sciences, 2003

Forbes.com (2009). Brain Imaging Study Sheds Light on Fibromyalgia. 19 June 2009, Accessed online on 1 July 2009 at http://www.forbes.com/feeds/hscout/2009/06/19/hscout628214.html

George, Hede Karyn (1996). Gene-Altered Mouse May Provide New Insights To Parkinson’s Disease, Substance Abuse And Schizophrenia. Bio-medicine. Accessed online on 1 July 2009 at http://news.bio-medicine.org/biology-news-2/Gene-Altered-Mouse-May-Provide-New-Insights-To-Parkinsons-Disease–Substance-Abuse-And-Schizophrenia-15585-1/

Gramling, C. (2006). Gender Gap: Male-Only Gene Affects Men’s Dopamine Levels. Science News, 169 (9): 4 March 2006, p. 132+

Hertel, P., Fagerquist, M.V., & Svensson, T.H. (1999). Enhanced cortical dopamine output and antipsychotic-like effects of raclopride by alpha-2 adrenoreceptor blockade. Science, 286, 105-107.

In Search of Madness: Schizophrenia and Neuroscience. Contributors: R. Walter Heinrichs – author. Publisher: Oxford University Press. Place of Publication: New York. Publication Year: 2001. Page Number: 157

Keltner, I. Norman; Hogan, Beverly and Guy, M. Dena (2001). Dopaminergic and Serotonergic Receptor Function in the CNS. Perspectives in Psychiatric Care. 37 (2): 2001, p. 65

Schulkin, Jay (2004). Bodily sensibility: intelligent action. Oxford University Press US, 2004

The Mail on Sunday (2008). How Drug Makes You Addicted to Sex and Betting.  6 July 2008, p. 22