Dopaminergic Pathway

Overview:

Dopamine is an excitatory neurotransmitter in the catecholamine family responsible for modulating reward and pleasure. It plays a key role in regulating emotional responses, the reward seeking processes and movement.

dopamine

Dopamine and Evolution

Dopamine is an evolutionarily ancient neurotransmitter that is found in both vertebrates and invertebrates.  Comparative phylogeny studies show us that there are several links between dopamine and behavioral responses subjected to reward (Barron, et. al, 2010). Many studies have suggested that the reward pathway has evolved from modulation of motor circuits in order to respond to environmental stimuli, eventually developing more specialized functions to avoid adverse stimuli or react to rewarding stimuli. There are several examples of genes that indicate conserved functions among vertebrates and invertebrates. For example, cyclic AMP-dependent protein kinase-related proteins affect learning and memory. However, it is still unclear if the role of dopamine is a conserved pathway or a product of convergent evolution.

Function of Dopamine in Different Phyla:

  • Cnidaria: affects mouth opening with food stimuli
  • Nematodes: modulates motor neurons in response to food stimuli
  • Mollusks: modulates motor neurons, affects reinforcement and reward learning
  • Insects: affects reinforcement and reward learning in conjunction with octopamine
  • Birds: development of learning and memory (ex. song/ vocalization in songbirds); working memory plasticity
  • Rodents: fear conditioning, positive/ negative reinforcement
  • Primates: reinforcement learning (error-reward feedback system)
  • Humans: reward, cognition, working memory, motor coordination, lactation

Dopamine Synthesis

Dopamine is a neurotransmitter that is synthesized in the brain itself.  This is because Dopamine cannot pass through the blood brain barrier.  Instead, a precursor to Dopamine, L-DOPA passes into the brain from he blood and is synthesized into Dopamine and other catecholamines.  This step by step process is described below:

Tyrosine Hydroxylase

  • Phenylalanine hydroxylase converts phenylalanine to tyrosine
  • Tyrosine hydroxylase converts tyrosine to L-DOPA
  • L-DOPA is converted to dopamine by aromatic amino acid decarboxylase
  • Dopamine can subsequently be converted to epinephrine or norepinephrine
  • Rate limiting enzyme: Tyrosine hydroxylase

Dopamine Receptor Types

There are 5 types of dopamine receptors (D1, D2, D3, D4, and D5), all of which are G-protein coupled receptors. These subtypes are further divided into 2 classes: D1R and D2R. D1R are post-synaptic and are generally considered to be excitatory. D2R are both pre-synaptic and post-synaptic and are inhibitory.  An overview of the main areas of activation of each receptor type is summarized below (Rang, 2001):

DA_rcpt_subtypes

Comparison of dopamine receptor types and function can be used to determine how the dopaminergic system evolved in different phyla.

Dopaminergic Pathways in the Brain and Associated Disorders:

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  • Mesolimbic Pathway: Dopamine is synthesized in the ventral tegmental area and transmitted into the limbic system via the nucleus accumbens.  This is generally referred to as the reward pathway of the brain.
    • Addiction is defined as  compulsive, habitual need to use a particular substance (cocaine, opium, nicotine, caffeine).
  • Mesocortical Pathway: Dopamine is synthesized in the ventral tegmental area and transmitted to the frontal cortex.  This pathway is associated with working memory, motivation and emotion.
    • Schizophrenia is a type of mental disorder that involves the breakdown of thought, emotion, and behavior resulting in inappropriate actions, such as withdrawal from relationships, delusions, mental fragmentation. This is caused by excess dopamine, hyper stimulation of D2R in the basal ganglia, and hypo stimulation of D1R in the frontal cortex. (Puig, et. al)
    • ADHD (Attention Deficit Hyperactivity Disorder) is characterized by inattentiveness, impulsivity, and hyperactivity. The size of the PFC is reduced in these patients, and genes in the dopaminergic pathway altered. (Puig, et. al)
    • Psychosis involves radical changes in personality, impaired functioning, and a distorted or nonexistent sense of objective reality.
  • Nigrostriatal Pathway: Dopamine synthesized in the substantia nigra pars compacta and transmitted to the dorsal striatum.  This pathway is associated with movement.
    • Parkinson’s disease is a movement disorder characterized by loss of muscle control resulting in tremors, loss of balance, and stiffness. It is caused by degenerate neurons in the substantia nigra pars compacta and decrease in phasic and tonic PFC dopamine levels. (Puig, et. al)
  • Tuberoinfundibular Pathway: Dopamine synthesized in the hypothalamus, stored in the pituitary.  This pathway regulates the secretion of the hormone prolactin from the anterior pituitary gland.

Dopamine Pathway Evolution

Evidence shows that dopamine first evolved as a neurotransmitter for movement, implicating the nigrostriatal pathway as the most ancestral of the four dopaminergic pathways.  However, the evolutionary history of the other pathways and their functions is not as clear.  We examine the evolutionary history and importance of two of these pathways, the mesolimbic and mesocortical pathways as they pertain to addiction and working memory respectively.  Which of these pathways has the more rich evolutionary history?  How did the behaviors associated with these pathways evolve throughout millions of years of selective pressures?  Answer these questions for yourself on the following pages!

 

References:

Barron, A., Søvik, E., & Cornish, J. (2010, October 12). The Roles of Dopamine and Related Compounds in Reward-Seeking Behavior Across Animal Phyla. Retrieved November 11, 2015, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2967375

Daubner, S., Le, T., & Wang, S. (2010, December 19). Tyrosine Hydroxylase and Regulation of Dopamine Synthesis. Retrieved November 11, 2015, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065393/

Jaber, M., Robinson, S., & Missale, C. (1996). Dopamine receptors and brain function. Retrieved November 11, 2015, from http://www.sciencedirect.com/science/article/pii/S0028390896001001
Puig, V., Rose, J., Schmidt, R., & Freund, N. (2014). Dopamine modulation in learning and memory in the prefrontal cortex: Insights from studies in primates, rodents, and birds.
Image Citations:

August 2015 Newsletter – Clayton Behavioral. (2015, August 17). Retrieved November 20, 2015, from http://claytonbehavioral.com/august-2015-newsletter/

Other transmitters and modulators. In: Pharmacology, 4th edition. Rang HP, Dale MM and Ritter JM. Edinburgh, UK: Harcourt Publishers Ltd, 2001:483–499. https://www.cnsforum.com/educationalresources/imagebank/dopaminergic/da_rcpt_subtypes

(n.d.). Retrieved November 20, 2015, from https://en.wikipedia.org/wiki/Dopamine