Neurotransmitter Systems III: Monoamines Flashcards
What are the monoamine systems involved in?
Motivation, reward, pleasure, movement, learning and cognition
What disorders can be caused by disregulation of the monoamine system?
Depression, schitzophrenia, Parkinson’s and Alzheimer’s
What are the central nervous systems that control behaviour?
Autonomic nervous system, hypothalamic-pituitary Neuro hormones and the diffuse monoamine system
What are the four main systems within the diffuse modulatory system?
Nor-adrenergic locus coeruleus
serotonergic raphe nuclei
dopaminergic substantia niagra and ventral tegmental
cholinergic basal forebrain and brain stem complexes
What are the common principles of the diffuse modulatory system?
Small set of neurons at the core,
Synapse from the brainstem
One neuron influences many others
Synapses release transmitter molecules into extracellular fluid
How are the GABA and glutamate pathways characterised?
Point to point communication that is fast and widespread
Give some examples of metabotropic receptors
5-HT1, 5-HT2, Dopamine D1, Dopamine D2, noradrenaline alpha 1 and 2
What does 5-HT1 do?
Inhibits AC
What does 5-HT2 do?
Stimulates PLC
What does dopamine D1 do?
Stimulates AC
What does dopamine D2 do?
Inhibits AC
What does noradrenaline beta do?
Stimulates AC
What does noradrenaline alpha1 do?
Stimulates PLC
What does noradrenaline alpha2 do?
Inhibits AC
Where is noradrenaline released from?
Adrenergic neurons that project from the locus coerulus
What are the functions of noradrenaline?
Arousal, wakefulness, exploration and mood, blood pressure and addiction
What is noradrenaline synthesised from?
Tyrosine
What are the steps in noradrenaline synthesis?
Tyrosine ->
DOPA ->
Dopamine ->
Noradrenaline
What enzyme converts tyrosine -> DOPA?
Tyrosine hydroxylase
What enzyme converts DOPA -> dopamine?
DOPA decarboxylase
What enzyme converts dopamine -> noradrenaline?
Dopamine beta-hydroxylase
How does reserpine work?
Depletes noradrenaline stores by inhibiting vesicular uptake
How do amphetamines work?
Enters vesicles displacing noradrenaline into the cytoplasm, which increases noradrenaline leakage out of the neuron into the synaptic cleft
What type of receptors are all adrenergic receptors?
GPCR
What are the noradrenergic receptors?
Alpha 1 and 2 and beta
What does the alpha 2 noradrenergic receptor work on?
Inhibits adenyl cyclase and calcium
What is noradrenaline broken down by inside the presynaptic neuron?
Monoamine oxidase
What happens if there isnt enough noradrenaline?
Depressed state?
What does too much noradrenaline cause?
Hyperaroused state
If there is an excess of noradrenaline, what happens?
Taken up into the presynaptic neuron and broken down by monoamine oxidase
What does cocaine block?
Noradrenaline reuptake
How can we increase noradrenaline availability?
Block noradrenaline transporter and inhibit monoamine oxidase
What is dopamine involved in?
Movement, reward, inhibition of prolactin release and memory consolidation
What are the different pathways for dopamine release?
Nigrostriatal, Mesolimbic, mesocortical and tubero-hypophyseal
Where does the nigrostriatal pathway project from and to?
Substantia nigra to the striatum
What is the nigrostriatal pathway involved in?
Movement
What disease affects the nigrostriatal pathway?
Parkinsons
Where does the mesolimbic pathway project from and to?
From the ventral tegmental area to many brain areas (nucleus accumbens, amygdala and hippocampus)
What is the mesolimbic pathway involved in?
Reward/pleasure
What does hyperactivity of the mesolimbic pathway lead to?
Schizophrenia
Where does the mesocortical pathway project from and to?
Ventral tegmental area to the frontal cortex
What is the mesocortical pathway involved in?
Executive function
What happens in the tubero-hypophyseal pathway?
Dopamine release from the hypothalamus into the pituitary
What does the tuberohypophyseal pathway cause?
Inhibition of prolactin release
What are the dopamine receptors in the chemoreceptor trigger zone involved in?
Triggering emesis
Which dopamine receptors are in the D1-like family?
D1 and D5
Which dopamine receptors are in the D2-like family?
D2,3 and 4
What does the D1-like receptor family do?
Stimulate adenyl cyclase
What does the D2-like receptor family do?
Inhibits adenyl cyclase and calcium influx and stimulates potassium efflux
Where are the D1 and D2-like receptor families found?
Post synaptically
Which is the only dopamine receptor to be found presynaptically?
D2
What happens if you have a dopamine excess?
Reuptake by dopamine transporters, where it will be broken down by monoamine oxidase B
How can you increase dopamine?
Give L-dopa
Block dopamine transporters
inhibit monoamine oxidase B
What is another name for serotonin?
5-HT
Where do the serotonin nerves project from?
Raphe nuclei to all over the brain
What do the serotonin nerves do in the hypothalamus?
Reduce appetite
What do the serotonin nerves do in the amygdala?
Elevate mood
What do the serotonin nerves do in the cortex?
Heightened perceptions
What do the serotonin nerves do in the spinal cord?
Suppress pain
How does ecstasy work?
Increasing serotonin
What is the synthesis pathway of serotonin?
Tryptophan ->
5-hydroxytrytophan ->
5-HT
What type of receptors are the serotonin receptors?
All GPCRs apart from 5HT3
Which is the only serotonin receptor to be found presynaptically?
5-HT 1D
What does 5-HT 1D activation do?
Inhibits serotonin release
What is acetylcholine involved in?
Memory, learning, motor control (striatum), reward and arousal
What are illnesses that are related with acetylcholine issues?
Alzheimer’s, pain, addiction, epilepsy, schizophrenia, ADHD, depression and anxiety
Where do cholinergic neurons project from?
Nucleus basalis, septum, substantia nigra
What is acetylcholine synthesised from?
Choline and acetyl CoA
Where are ACh receptors found?
Both pre and postsynaptically
What enzyme breaks ACh down?
Acetylcholine esterase
What are the functions of histamine?
Sleep/wake and vomiting
What are the functions of purines?
Sleep, pain, neuroprotection, addiction, seizures
What are the functions of Neuro peptides?
Pain
What are lipid mediators products of?
Conversion of eicosanoids to endocannabinoids
What do lipid mediators act on?
CB1
What is melatonin involved in?
Sleep regulation, circadian rhythm
What are the theraputic uses of amphetamines?
ADHD
What are the pharmacological effects of amphetamines?
Increased alertness and locomotor stimulation, euphoria, stereotyped behaviour, anorexia, decreased physical and mental fatigue, lack of tiredness
What does cocaine do?
Blocks the dopamine transporters
What are the pharmacological effects of cocaine?
Euphoria, locomotor stimulation, heightened pleasure
How does MDMA work?
Inhibits monoamine transporters
What does MDMA cause?
Increased serotonin and dopamine
How does LSD/psilocybin work?
Hallucinogenic effect by acting on 5HT2 receptors