Neurotransmitter Systems III : Monoamines Flashcards
What are the CNS systems that control behaviour?
→ Autonomic nervous system
→ Hypothalamic-pituitary neurohormones
→ Diffuse monoamine systems
What are examples of monoamines?
→ Noradrenaline
→ Serotonin
→ Dopamine
→ ACh
What neurons project from the central core?
→ Adrenergic
→ Serotonergic
→ Dopaminergic
→ Cholinergic
What are the four systems with common principles?
→ Small set of neurons at the core
→ Arise from the brain stem
→ One neuron influences many others
→ Synapses release transmitter molecules into extracellular fluid
What is the main source of noradrenergic neurons in the brain?
→ Locus Coeruleus
What is the main source of serotonergic neurons in the brain?
→ Raphe Nuclei
What are the main sources for the dopaminergic neurons in the brain?
→ Substantia nigra
→ Ventral tegmental area
What are the main sources for cholinergic neurons in the brain?
→ Basal forebrain and brain stem complexes
What 3 things are involved in fast point-to-point signalling? (type of channel and transmitter)
→ Neurotransmitters producing excitatory or inhibitory potentials
→ Ligand gated ion channels
→ Glutamate, GABA, ACh
What 3 things are involved in slow transmission?
→ Neurotransmitters and neuromodulators
→ G-Protein coupled receptors
→ Monoamines, peptides, ACh
Where do noradrenergic neurons project from?
→ Central core
What 5 areas of the brain do noradrenergic neurons project to?
→ Cortex → Amygdala → Hypothalamus → Spinal cord → Cerebellum
What is the locus coerulus involved in?
→ Making the brain more responsive
→ Information processing
What is noradrenaline involved with?
→ Gambling
What are withdrawal symptoms driven by?
→ Hyperexcitability from noradrenaline
What receptors does noradrenaline act on?
→ G coupled post-synaptic receptors
→ activates presynaptic alpha 2 receptors
What are noradrenergic alpha 2 receptors also called and why?
→autoreceptors
→ When noradrenaline binds it inhibits the release of noradrenaline
What do low levels of noradrenaline lead to?
→ Depression like behaviour
How is the action of noradrenaline terminated?
→ Inside the membrane there are NET transporters
→ Uptake excess noradrenaline inside the neuron
→ Once inside they get broken down by monoamine oxidase
How do amphetamines work?
→ They enter vesicles and displace the NA into the cytoplasm which causes NA leakage out of the neuron
What does cocaine do?
→ Blocks NA reuptake
What is the main action of noradrenaline?
→ Inhibitory ( alpha 2)
→ Also excitatory (alpha/beta)
How is noradrenaline terminated?
→ Neuronal uptake
→ MAO
What is the main cell body of noradrenaline?
→ Locus coerulus
When are noradrenergic neurons active?
→ When awake
Where are high densities of noradrenergic neurons found?
→ Brainstem
→ Hypothalamus
→ Medial temporal lobe
What are the functions of noradrenergic neurons?
→ Arousal
→wakefulness
→ mood
→ Blood pressure regulation
Describe the nigrostriatal pathway?
→ Dopaminergic neurons project from the substantia nigra to the striatum
Why does Parkinsons occur?
→ Dopaminergic neurons become degenerated
Describe the mesolimbic pathway?
→ Dopaminergic neurons project from the ventral TA to
→ amygdala
→ Hippocampus
→ Nucleus Accumbens
What is the function of the nucleus Accumbens?
→ Rewards and pleasure
What is schizophrenic behaviour due to?
→ Hyperactivity of the mesolimbic pathway
Describe the mesocortical pathway?
→ Dopaminergic neurons projecting from the VTA to the cortex
Describe the tuberohypophyseal pathway?
→ Dopamine is released from the hypothalamus directly to the circulation
In what situation does dopamine act as a neurohormone?
→ It goes to the anterior pituitary and inhibits the release of prolactin
What receptors are activated during emesis?
→ D2 receptors
Describe the formation of dopamine?
→Tyrosine gets metabolised by tyrosine hydroxylase
→ this forms DOPA
→ DOPA gets metabolised by DOPA decarboxylase to form dopamine
What receptors does dopamine act on?
→ D1 and D2
What kind of receptors are D2 receptors and where are they found?
→ Pre and post synaptically
→ Autoreceptors
What is the function of D2 receptors?
→ WHen dopamine binds to the autoreceptors they inhibit the release of dopamine
What breaks down dopamine?
→ Monoamine oxidase
What do low and high levels of dopamine lead to?
→ High - Schizophrenia
→ Low - Depression
What is a way to treat parkinsons?
→ Blocking the reuptake of dopamine
→ Stopping monoamine oxidase
What is a way to treat schizophrenia?
→ Blocking dopamine receptors
What is the D1 receptor coupled with?
→ Gs couples receptors
What is the D2 receptor coupled with?
→ Gi coupled receptor
Where are D1 and D2 receptors found?
→Striatum
→ Limbic system
→ Thalamus
→ Hypothalamus
Where are D3 receptors found?
→ Limbic system
Where are D4 receptors found?
→ cortex and limbic system
What are the functions of dopamine?
→ Movement
→ Addiction
→ Hormone release
→ Vomiting
Where do serotonergic neurons project from?
→ Raphe Nuclei
Where do serotonergic neurons project to?
→ Cortex → Cerebellum → Striatum → Hypothalamus → Hippocampus → Amygdala
What does serotonin increase in the cortex lead to?
→ Heightened perception
What does serotonin increase in the hypothalamus lead to?
→ Reduced appetite
What does serotonin increase in the amygdala lead to?
→ Elevated mood and emesis
What drugs increase serotonin?
→ Antidepressants
→ Ecstasy
Describe the formation of Serotonin?
→ Tryptophan gets metabolised by tryptophan hydroxylase
→ this forms 5 hydroxytryptophan
→ 5 hydroxytryptophan gets metabolised into serotonin
What does too much serotonin lead to?
→ Psychotic like effects
What does too little serotonin lead to?
→ Depression effects
What do antidepressants block?
→ SERT reuptake
What does activation of 5-HT 1D receptor lead to?
→ Inhibition of serotonin
→ Autoreceptor
What metabolizes serotonin?
→ MAO
How many serotonin receptor subtypes are there?
→ 14
What is the 5-HT1 receptor for?
→ mood
→ Migraine
→ autoreceptor
What are the excitatory serotonin receptors?
→ 5HT2
→ 5HT3
What is the function of serotonin?
→ Mood → Psychosis → Sleep/wake → Feeding behaviour → Pain → Migraine
What are the 3 cholinergic neuron pathways?
→ Nucleus basalis to the cortex
→ Septum to the hippocampus
→ Substantia nigra to the thalamus
Where are cholinergic interneurons found?
→ in the striatum
Why do people suffer from memory impairment?
→ Degeneration of cholinergic neurons
What are the two kinds of Ach receptors?
→ Nicotinic
→ Muscarinic
How is ACh formed?
→ Acetyl CoA and choline join
Where are ACh receptors found in the brain?
→ Basal forebrain
→ Hippocampus
→ Striatum
What is the function of Ach?
→ Arousal
→ Epilepsy
→ Learning and memory
→ Motor control
What are the functions of histamine?
→ sleep
→ Wake
→ vomiting
What are the functions of purines?
→ Sleep → pain → Neuroprotection → Addiction → Seizures → anti convulsant
What are the functions of neuropeptides?
→ Pain
What is melatonin involved in?
→ sleep regulation
→M1 and M2
What are the effects of amphetamine?
→ Alertness
→ Euphoria
→ Anorexia
→ Confidence / lack of tiredness
What does prolonged use of amphetamines cause?
→ Neurotoxicity
→ Degeneration of amine containing nerve terminals
→ Cell death
What does cocaine increase?
→ Dopamine
→ Noradrenaline
→ Serotonin
What happens to transporters when you take cocaine?
→ blockades of dopamine transporters
→ accumulates in the cleft
What are the metabotropic receptors for the monoamines?
→ noradrenaline - beta - stimulates adenylyl cyclase -alpha 1 - stimulates PLC -alpha 2 - inhibits adenylyl cyclase → dopamine D1- stimulates adenylyl cyclase D2 inhibits adenylyl cyclase → Serotonin 5-HT1 - inhibits adenylyl cyclase 5-HT2 stimulates pLC
What is the effect of reserpine?
→ Depletes NA stores by inhibiting vesicular uptake
What are the 5-HT receptor functions? (1-7)
→ 5HT1 - inhibitory - limbic system - mood → 5HT2 - excitatory - limbic → 5HT3 - excitatory- medulla - vomiting → 5HT4 - presynaptic faciliation → 5HT 6 -7 - sleep
What are the neurotransmitter transporter?
→ dopamine - DAT → 5-HT - SERT → NA - NET → glutamate - EAAT1 → dopamine - VMAT2 (vesciles)
What are the functions of ACh receptors (M1-M3)
→ M1 - excitatory
→ M2 presynaptic inhibition
→ M3 - excitatory glandular/smooth muscle effects
