Continuing to explore the cause of excess Dopamine

Parkinson’s Disease and Tourette’s Syndrome

This is an interesting post which analyzes the excess of dopamine as the source of involuntary movements

Indeed, involuntary movements, commonly referred to as tics, are the primary symptoms of a disease called Tourette’s Syndrome. The syndrome, named after the person who first described it, Gilles de la Tourette, “is a complex neurobehavioral disorder characterized by motor tics (quick, involuntary movements that occur out of a background of normal motor activity).” (4) As to substantiate the postulation made above, Tourette’s Syndrome should be the result of increased dopamine or enhanced dopamine effects in the relevant areas of the brain, i.e. where movement is planned or motor behavior is organized. Surely enough, research done on the basal ganglia, namely the striatum and the caudate nucleus, has revealed that dopamine indeed impacts on these areas more prominently in Tourette’s patients than in unaffected controls. (5,6) The increased dopamine effect in Tourette’s patients may be due to two mechanism. One, the patients may produce more dopamine, hence, their receptors are over-stimulated, leading to excessive neuronal firing, in turn leading to involuntary movements. However, this theory seems to not hold, as presumably neurons would activate compensatory mechanism to deal with the increase in neurotransmitter concentration. If really dopamine was present in excess, one would expect receptor sites to down-regulate. One can assume that dopamine is not present in excess in Tourette’s patients. A second mechanism has been proposed. According to this, the dopamine levels in Tourette’s patients are equivalent to non-patients, but their receptor sites are supersensitive. This theory seems to hold true and has been successfully confirmed in the laboratory. Research surrounding dopamine binding in implicated structures of the brain yielded, “that binding to D2 dopamine receptors in the caudate nucleus was higher in the sibling with the more severe symptoms. ‘Strikingly, the degree to which the twins differed in this caudate D2 binding predicted almost absolutely their difference in tic severity.'” (5) Hence, the study supports the role of dopamine and explicates why Tourette’s are subject to increased dopamine effects.

Symptoms of Excess Dopamine or Taurine

In amounts normally produced by the body, dopamine functions as a minor brain stimulant that primarily controls movement, and to a lesser degree blood circulation and metabolism. Dopamine also acts as a stimulant to the pleasure center of the brain. Symptoms of excess dopamine are similar to the effects of the chemicals itself, only more severe. These symptoms include increased movement/jittery feelings, dangerously increased rate of metabolism and recklessness caused by overstimulation of the pleasure center of the brain.

The Dopamine Theory

In 1963, researchers Carlsson and Lindqvist proposed The Dopamine Theory. Dopamine is a brain neurotransmittor and is believed to be an inhibitor of a person’’s functions. It is speculated that an abnormality in the brain processes causes there to be an excess of dopamine which leads the brain to autointoxicate itself causing the symptoms of schizophrenia to emerge. This excess of dopamine could result from the schizophrenia-prone brain secreting an abundance of dopamine, the schizophrenic brain containing an abnormally high amount of dopamine receptors, or the receptors being hypersensitive to the normal secretions of the brain. There is also evidence that some schizophrenics have a lower than normal level of an enzyme that is meant to break down dopamine. This overproduction of dopamine causes the nerve circuits to misfire and create a split state in the mind where delusions and hallucinations make the reality of the outside world easier to accept.

[[QQQ: Need to learn more about what receptors are present in the Basal Ganglia (D1-D2) and what would make them become hypersensitive. Need to understand in general what receptors are, why the sensitivity changes and if the sensitivity change is reversable. Need to also understand what is the enzyme which usually breaks down dopamine and see if somehow people with 22q11 micro-deletion are less able to perform this transformation (this is what one of last nights’ article was pointing to)]].

Normal Dopamine Neurotransmission

The Brain–Emotions, Neurons, Neurotransmitters

There are 100 Billions Neurons in the brain. Each neuron is has up to 50,000 connections.

Synaptic Transmission

Slightly more detailed. Includes the role of enzyme with regards to neurotransmitters.

Dopamine in Wikipedia

Abnormally high dopaminergic transmission has been linked to psychosis and schizophrenia.[54] Increased dopaminergic functional activity, specifically in the mesolimbic pathway, is found in schizophrenic individuals. Anti-psychoticmedications act largely as dopamine antagonists, inhibiting dopamine at the receptor level, and thereby blocking the effects of the neurochemical in a dose-dependant manner. The older, so-called typical antipsychotics most commonly act on D2 receptors,[55] while the atypical drugs also act on D1, D3 and D4 receptors.[56][57] The finding that drugs such as amphetamines, methamphetamine and cocaine, which can increase dopamine levels by more than tenfold,[58] can temporarily cause psychosis, provides further evidence for this link.[59]

Basal Ganglia in Wikipedia

In most regions of the brain, the predominant classes of neurons use glutamate as neurotransmitter and have excitatory effects on their targets. In the basal ganglia, however, the great majority of neurons use GABA as neurotransmitter and have inhibitory effects on their targets. The inputs from the cortex and thalamus to the striatum and STN are glutamatergic, but the outputs from the striatum, pallidum, and substantia nigra pars reticulata all use GABA. Thus, following the initial excitation of the striatum, the internal dynamics of the basal ganglia are dominated by inhibition and disinhibition.

Other neurotransmitters have important modulatory effects. The most intensively studied is dopamine, which is used by the projection from the substantia nigra pars compacta to the striatum, and also in the analogous projection from the ventral tegmental area to the nucleus accumbens. Acetylcholine also plays an important role, being used both by several external inputs to the striatum, and by a group of striatal interneurons. Although cholinergic cells make up only a small fraction of the total population, the striatum has one of the highest acetylcholine concentrations of any brain structure.

Disrupted Dopaminergic Neurotransmission in 22q11

It [the COMT gene] encodes an enzyme that is important for the breakdown of catecholamines, including dopamine (DA) and norepinephrine (NE). The gene is expressed in all regions of the human central nervous system, but the enzyme is particularly important for DA clearance in the prefrontal cortex (PFC)

[[ QQQ Now that I understand what neurons, synapses, neuro-transmittors and receptors are, I need to understand how a gene encodes an enzyme and how/when an enzyme breaksdown dopamine. I also need to understand what is the blood brain barrier ]]

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One Response to Continuing to explore the cause of excess Dopamine

  1. caroline says:

    Wow….thank you for sharing all of this. I am passionate about the material and our Cala.

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