Dopamine - Expanded Flashcards
What compound is the precursor to dopamine?
L-DOPA.
How can dopaminergic neurones be identified electrophysiologically?
They can be seen to exhibit tonic/burst firing.
Which inputs control the firing of dopaminergic neurones?
Inputs from the cortex (Glu), SNr (GABA), Raphe (5HT), Locus coeruleus (NA).
How does the firing of dopaminergic neurones change when they are assayed in brain slices?
They tick over at a rate of 6 times per second as they have lost their inputs so have lost their burst fire potential.
How is dopamine released at classical synapses?
By calcium-dependent exocytosis.
Name the three central dopaminergic pathways.
The nigrostriatal system, the mesolimbic/mesocortical pathways, and the tuberohypophyseal system.
Where do the nerves of the nigrostriatal system originate from and where do they link to?
The nerves of the nigrostriatal system originate in the A9 cell group of the substantia nigra and link to the corpus striatum.
What functions is the nigrostriatal system involved in?
Motor control and motor planning.
What does a loss of dopamine in the nigrostriatal system lead to?
Loss of movement (akinesia) or reduced movement (dyskinesia).
In animal experiments, what do unilateral 6-OH dopamine legions result in?
Contralateral turning, the animal turns towards the lesioned site.
Parkinson’s disease is associated with a deficiency in which central dopaminergic pathway?
Nigrostriatal.
Where do the nerves of the mesolimbic/mesocortical systems originate from and where do they link to?
The nerves of the mesolimbic/mesocortical systems originate from the A10 nerve group in the ventral tegmental area ad link to the nucleus accumbens, amygdala, and cortex.
What are the mesolimbic and mesocortical pathways responsible for?
They are responsible for motivation, behavioural control, cognition, and addiction.
What is the result of a large amount of dopamine in the mesolimbic/mesocortical systems?
Stereotyped repetitive behaviours indicative of psychosis or schizophrenia.
What is a common side effect of over administration of parkinson’s medication?
Schizophrenic symptoms due to an increase of dopamine in the mesolimbic/mesocortical systems.
Symptoms of what disease can be seen in schizophrenic patients given an excess of dopamine receptor antagonists?
Parkinson’s.
Where do the nerves of the tubero-hypophyseal system originate from and where do they link to?
The nerves of the tubero-hypophyseal system originate in the A12 nerve group of the arcuate nucleus of the hypothalamus and link to the medial eminence and the pituitary gland.
Which neurotransmitter controls hormone release from the anterior pituitary gland?
Dopamine.
What hormone does dopamine inhibit the release of?
Prolactin.
What hormone does dopamine increase the release of?
Growth hormone.
How do anti-psychotic D2 antagonists cause gynecomastia (breast development in men) and male lactation?
They prevent dopamine from inhibiting prolactin release.
Where does dopamine also act to cause nausea and vomiting?
The chemo-receptor trigger zones in the medulla.
Where does dopamine act to cause dilation of blood vessels?
Vascular smooth muscle.
How does reserpine act to prevent dopamine from being converted to noradrenaline?
It blocks dopamine uptake into vesicles.
What is the main mechanism for dopamine signal termination?
Re-uptake in synaptic terminals by specific dopamine transporters.
What illicit drug blocks dopamine reuptake?
Cocaine.
What enzymes enzymatically degrade dopamine? What is it degraded into?
MAO, COMT, and aldehyde dehydrogenase. It is degraded into dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA)
DOPAC and HVA are excreted in the urine, what can this be used as a measure of?
Dopamine release.
What form of receptors are all dopamine recetors?
Metabotropic; GPCRs.
What are the two types of dopamine receptors?
D1 like and D2 like.
What cellular effect does activation of D1 like dopamine receptors have?
An increase in adenylate cyclase activity leading to an increase in cAMP.
What cellular effect does activation of D2 like dopamine receptors have?
A decrease in the activity of adenylate cyclase leading to a decrease in cAMP. This leads to an increase in potassium ion influx and a decrease in cellular calcium ion concentration.
What is the potency of dopamine to D1 like receptors?
Low.
What is the potency of dopamine to D2 like receptors?
High.
Which two types of dopamine receptors are the most common?
D1 and D2.
Where are D1 and D2 dopamine receptors found most commonly?
In all terminal fields.
Where are D3 and D4 dopamine receptors found most commonly?
In limbic areas.
Where are D5 dopamine receptors only found?
In the hippocampus, hypothalamus, and thalamus.
What conditions can be treated by targeting dopaminergic pathways?
Schizophrenia, ADD, drug dependence, endocrine dysfunctions, movement disorders (Parkinson’s).
