Dopamine Flashcards
What are the primary neurotransmitters?
Glutamate and GABA - the mainworkhorses of the brain. Directly mediate the transition of information between neurons either via activation or inactivation
What are neuromodulators?
These affect the response properties of a neuron - don’t carry primary information themselves e.g. dopamine, serotonin, noradrenaline, acetylcholine
if u have these, neuron may fire more, less, or at different frequencies
Can neurotransmitters be neuromodulators and vice versa?
Some neurotransmitters act as neuromodulators - GABA at GABAa receporos
some neuromodulators act as neurotransmitters ach at nicotinic ACh receptors
What are the diffuse modulatory systems?
Specific populations of neons which project diffusely and modulate the activity of glutamate and gaba in their target areas: dopamine, serotonin, noradrenaline and acetylcholine
5 steps of regulation of neurotransmitter
- Neurotransmitter is synthesized
- Neurotranmitter is packaged into vesicles
- Neurotransmitter is released when vesicles fuse
- Neurotransmitter binds to and activates post synaptic receptors
- Neurotransmitter diffuses away and is transported back
What is dopamine involved n?
Motivation and reward
Addiction
Movement
Where are dopamine neurones?
Cell bodies in the midbrain
Project into the forebrain
What are the 3 dopamine systems?
Nigrostriatal system
Mesolimbic system
Mesocortical system
Where projections occur in the nigrostriatal system?
Substantia nigra projections to neostriatum
What is the nigrostriatal system involved in?
Role in movement
What does dysfunction of the nigrostriatum system lead too?
Parkinsons disease - destruction of DA projections from SN to basal ganglia
Huntingdons - destruction of DA target neurons in striatum
Where projections occur in the mesolimbic system?
Ventral tegmental area projection to the nucleus accumbens
What is the mesolimbic system involved in?
Reward
What does dysfunction of the msolimbic system result in?
Addiction - most drugs of abuse lead to enhanced DA release in the NaCC
What projections occur in the mesocortical system?
VTA projections to the prefrontal cortex
What is the mesocortiyal system involved in?
Working memory and planning
What does dysfunction in the mesocortical system lead too?
Schizophrenia / depression
How is dopamine synthesised?
Tryosine (amino acid which comes from diet) is catalysed (made) by tyrosine hydroxyls (TH) - rate limiting, slowest step
L DOPA is then made, which is catalysed by dopa decarboxylase
Leading to dopamine
What happens when dopamine is synthesised?
It is stored in the vesicles
How is dopamine controlled?
By regulating tyrosine hydroxlyase activity - controls amount of dopamine available for release
What are the 3 ways that dopamine is controlled?
- Feedback inhibition by end products - dopamine competes for binding with a cofactor, which pushes it out, too much dopamine lowers TH activity - Down regulation of synthesis
- Presynaptic activity (DA release) leads to phosphorylation of TH (via autoreceptor) which increases its activity - Up regulation
- Prolonged activity in the presynaptic neuron leads to an increase in transcription of the TH gene leading to more enzyme synthesized - Up regulation
What does transcription mean?
Changing RNA to protein
What drugs affect dopamine synthesis and storage?
Reserpine - impairs the storage of monoamines (what dopamine comes from) in synaptic vesicles - so they are empty, resulting in no dopamine release
L - DOPA - the precursor of dopamine, bypasses rate limiting TH step, converts it into dopamine so increasing the pool
AMPT - inactivates TH - only used experimentally, not in treatment
What can L dopa treat?
Parkinsons disease - most effective drug, but as the disease progresses, give more L dopa - at some point, it will stop working
side effects: can develop gambling issues
