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Neuro Science    

 

 

 

Dopaime Pathways

Dopamine pathway is a kind of neural connections (a neural pathway) which is mediated by the neurotransmitter dopamine. In other words, The dopamine pathway is a critical neural pathway in the brain that involves the transmission of the neurotransmitter dopamine from one region of the brain to another.

 A nervous system (e.g, our brain) is not a bunch of functional bricks mechanically sticking together. There are huge numbers of interconnections from one part to another part. Through those interconnection (synapses), the nerve signal traverse from a neuroto next neuron. When multiple neurons are connected together and form a pathway (or circuit) to perform a specific function, we call it a neural pathway. Dopamine pathway is a type of this neural pathways. The major neurotransmitters in the synapse along the pathway is dompamine. That's why it is called a dompamine pathway. Of course, there are so many different types of neural pathways mediated by different types of neurotransmitters and have different names. In this note, I would mostly focus on domapine pathway.

Overview

There are multiple dopamine pathways (4 or 5 well known pathways) which are involved in functions as follows.

  • executive thinking / decision making
  • cognition
  • feelings of reward and pleasure
  • voluntary motor movements

I personally interested in 'reward and pleasure' part and that is why I decided to write a note for domapine pathway. However, 'reward and pleasure' is only one of several pathways mediated by dopamine and  you may have different interest on your own.  Well known dopamine pathways are illustrated as below.

Mesolimbic Dopamine Pathways

The mesolimbic dopamine pathway is a neural circuit that originates in the midbrain and projects to various regions of the brain, including the nucleus accumbens, the olfactory tubercle, and the prefrontal cortex. This pathway is known to play a key role in reward processing and is activated when animals (including humans) experience pleasurable or rewarding stimuli, such as food, sex, or drugs of abuse. Activation of this pathway leads to the release of dopamine in the nucleus accumbens, which is thought to contribute to the pleasurable or rewarding effects of these stimuli.

The mesolimbic dopamine pathway is also thought to play a role in various psychiatric and neurological disorders, such as addiction, schizophrenia, and Parkinson's disease. For example, drugs of abuse are known to increase dopamine release in the nucleus accumbens and other regions of the mesolimbic pathway, which is thought to contribute to their addictive properties. Additionally, dysfunction or abnormal activity in this pathway has been implicated in the positive symptoms of schizophrenia, such as hallucinations and delusions, as well as in the negative symptoms, such as apathy and lack of motivation.

The characteristics of this pathway

  • Function :pleasure and reward
  • Path : From ventral tegmental area (VTA) to nucleus accumbens (NAc).
  • NAc mediates feelings of pleasure and reward
  • Triggers : Any kinds of rewarding / pleasure stimuli e.g,  food, sex, drugs, etc
  • Stimulation of the NAc is important for maintaining our day-to-day activity. However, over-stimulation can lead to cravings for the item that stimulated the NAc.

Conditions that may cause problems in this pathway :

  • Addiction. Drugs of abuse, such as opioids, cocaine, and amphetamines, are known to increase dopamine release in the nucleus accumbens and other regions of the mesolimbic pathway, which is thought to contribute to their addictive properties. This increase in dopamine release leads to a reinforcement of drug-seeking behavior and an overall change in the reward system of the brain, making it more difficult to quit the drug.
  • Schizophrenia. Dysfunction in this pathway has been implicated in the positive symptoms of schizophrenia, such as hallucinations and delusions, as well as in the negative symptoms, such as apathy and lack of motivation. Some of the antipsychotic drugs used to treat schizophrenia are thought to work by blocking dopamine receptors in the mesolimbic pathway.
  • Depression.  Depression is related to the reward system, and depression is characterized by anhedonia, a loss of pleasure, which is thought to be linked to dysfunction in this pathway.
  • Parkinson's disease, Parkinson's disease is a neurodegenerative disorder characterized by tremors, stiffness, and difficulty initiating movement, also related to the mesolimbic dopamine pathway as the degeneration of dopamine neurons in the substantia nigra, a brainstem area, leads to a reduction of dopamine levels in the mesolimbic pathway, which results in cognitive and emotional impairments.

Mesocortical Dopamine Pathways

The mesocortical dopamine pathway is a neural circuit that originates in the midbrain and projects to various regions of the brain, including the prefrontal cortex, the anterior cingulate cortex, and the hippocampus. This pathway is known to play a role in cognitive and emotional processing, and is thought to be involved in a wide range of behaviors and functions, such as attention, working memory, decision-making, and emotion regulation.

Like the mesolimbic dopamine pathway, the mesocortical pathway is thought to be involved in various psychiatric and neurological disorders. For example, dysfunction or abnormal activity in this pathway has been implicated in the negative symptoms of schizophrenia, such as apathy and lack of motivation, as well as in the cognitive symptoms, such as working memory deficits and attentional impairments. Additionally, the mesocortical pathway is thought to be involved in the development of addiction, as drug-induced changes in dopamine activity in this pathway are thought to contribute to the compulsive drug-seeking behavior seen in addiction.

It is also thought to play a role in Parkinson's disease, as the degeneration of dopamine neurons in the substantia nigra, a brainstem area, leads to a reduction of dopamine levels in the mesocortical pathway and other dopamine pathways, which results in cognitive and emotional impairments.

The characteristics of this pathway

  • Function : cognition, working memory, and decision making  
  • Path : From ventral tegmental area (VTA) to nareas in the prefrontal cortex (PFC).
  • when you have problem (dysfunction) in this path, you may experience poor concentration and the inability to make decisions

Conditions that may cause problems in this pathway :

  • Schizophrenia. Dysfunction or abnormal activity in this pathway has been implicated in the negative symptoms of schizophrenia, such as apathy and lack of motivation, as well as in the cognitive symptoms, such as working memory deficits and attentional impairments. Antipsychotic drugs, which are used to treat schizophrenia, are thought to work by blocking dopamine receptors in the mesocortical pathway.
  • Addiction. The mesocortical pathway is thought to be involved in the development of addiction, as drug-induced changes in dopamine activity in this pathway are thought to contribute to the compulsive drug-seeking behavior seen in addiction.
  • Depression. Depression is also related to the mesocortical dopamine pathway, as it is related to the regulation of emotion and cognition, and depression is characterized by anhedonia, a loss of pleasure, which is thought to be linked to dysfunction in this pathway.
  • Parkinson's disease. Parkinson's disease is a neurodegenerative disorder characterized by tremors, stiffness, and difficulty initiating movement, also related to the mesocortical dopamine pathway as the degeneration of dopamine neurons in the substantia nigra, a brainstem area, leads to a reduction of dopamine levels in the mesocortical pathway and other dopamine pathways, which results in cognitive and emotional impairments.

Nigrostriatal Dopamine Pathways

The nigrostriatal dopamine pathway is a neural circuit that originates in the substantia nigra, a brainstem area, and projects to the striatum, a subcortical brain region that is involved in motor control, reward and learning. The main role of the nigrostriatal dopamine pathway is to control movement, specifically the initiation and execution of voluntary movements.

The substantia nigra, which is located in the midbrain, contains dopamine-producing neurons that project to the striatum. These neurons release dopamine into the striatum, which then binds to dopamine receptors on the neurons there. This binding of dopamine to the receptors leads to changes in the activity of the neurons in the striatum, which in turn leads to changes in movement.

Damage to the dopamine neurons of the substantia nigra is a primary cause of Parkinson's disease, a progressive disorder of the nervous system characterized by tremors, stiffness and difficulty in initiating movement. Parkinson's disease is caused by the degeneration or death of dopamine-producing neurons in the substantia nigra, which leads to a reduction in dopamine levels in the striatum and other dopamine pathways. This results in a loss of dopamine-mediated control of movement, leading to the motor symptoms of the disease.

The characteristics of this pathway

  • Function : motor planning
  • Path : From the substantia nigra to the caudate and putamen, parts of the basal ganglia..
  • this pathway stimulate purposeful movement. Reduced numbers of dopamine neurons in this pathway is a major aspect of motor control impairmen
  • This pathway contains around 80% of dopamine in the brain.

Conditions that may cause problems in this pathway :

  • Parkinson's disease . Parkinson's disease is a progressive disorder of the nervous system characterized by tremors, stiffness and difficulty in initiating movement. Parkinson's disease is caused by the degeneration or death of dopamine-producing neurons in the substantia nigra which leads to a reduction in dopamine levels in the striatum and other dopamine pathways. This results in a loss of dopamine-mediated control of movement, leading to the motor symptoms of the disease.
  • Parkinsonian-plus syndromes . Parkinsonian-plus syndromes are a group of disorders characterized by Parkinsonism symptoms and additional symptoms such as dementia, ataxia, or dystonia.
  • Drug-induced Parkinsonism . Drug-induced Parkinsonism is a side effect of drugs, such as antipsychotics, metoclopramide, and prochlorperazine.
  • Wilson's disease (a Genetic disorder) . Wilson's disease is a rare inherited disorder that causes an accumulation of copper in the liver, brain, and other vital organs
  • Huntington's disease(a Genetic disorder) . Huntington's disease is a genetic disorder that causes the progressive breakdown of nerve cells in the brain

Tuberoinfundibular Dopamine Pathways

The tuberoinfundibular dopamine pathway (TIDA) is a neural circuit that originates in the hypothalamus and projects to the pituitary gland. This pathway is known to play a role in the regulation of hormone release, specifically the control of prolactin secretion from the pituitary gland.

Prolactin is a hormone that stimulates milk production in women and plays a role in other physiological processes such as the regulation of the menstrual cycle, immune system and growth. The release of prolactin from the pituitary gland is controlled by a delicate balance between the stimulating effect of hypothalamic hormones like thyrotropin-releasing hormone (TRH) and the inhibitory effect of dopamine, which is secreted by the TIDA pathway.

Dopamine released by the TIDA pathway acts on dopamine D2 receptors in the pituitary gland to inhibit prolactin release. This is why drugs that increase dopamine activity in the TIDA pathway, such as dopamine agonists, are often used to treat hyperprolactinemia, a condition characterized by high prolactin levels and associated with symptoms such as infertility, galactorrhea (breast milk production) and menstrual irregularities.

The characteristics of this pathway

  • Function :inhibit prolactin release
  • Path : From arcuate and periventricular nuclei of the hypothalamus to the infundibular region of the hypothalamus, specifically the median eminence
  • Prolactin is a protein secreted by the pituitary gland that enables milk production and has important functions in metabolism, sexual satisfaction and the immune system.

Conditions that may cause problems in this pathway :

  • Hyperprolactinemia. Hyperprolactinemia is a condition characterized by high prolactin levels and associated with symptoms such as infertility, galactorrhea (breast milk production) and menstrual irregularities. Hyperprolactinemia can be caused by dysfunction or abnormal activity in the TIDA pathway, such as low dopamine levels, which can be caused by a variety of factors such as pituitary tumors, medications and some medical conditions.
  • Pituitary tumors. Specifically prolactinomas, benign tumors that produce prolactin and that affect the TIDA pathway.
  • Drug-induced hyperprolactinemia , This is caused by drugs that block the activity of dopamine in the TIDA pathway, such as antipsychotics, antidepressants, and some anti-hypertensive medications, can also cause problems in the TIDA pathway.
  • Prader-Willi syndrome.  Prader-Willi syndrome is a genetic disorder that affects many parts of the body and it can cause hyperprolactinemia and affects the TIDA pathway.

Reference

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