Monoamines Flashcards
What are the 4 diffuse modulatory monoamine systems of the brain?
Noradrenergic - Locus Coeruleus
Sertonergic - Raphe Nuclei
Dopaminergic - Substantia Nigra and ventral tegmental area
Cholinergic - Basal Forebrain and Brain Stem Complexes
What are the effects of NA?
Arousal and wakefulness
Exploration and mood
Blood pressure rise following stress
Addiction due to increase excitement and arousal
How is NA synthesised and what regulates it?
Tyrosine → DOPA via tyrosine hydroylase → Dopamine via DOPA decarboxylase → NA via dopamine B-hydroxylase
autoregulated by auto-receptor alpha-2 on presynaptic membrane which stops Ca2+ activity
NA is also removed from cleft via NA-transporters and broken down by monamine oxidase (MAO)
What are the 3 NA receptors and what are their actions?
a1 - Gq: PIP2 → DAG + IP3 = ↑Ca2+ = smooth muscle contraction, glycogenolysis
a2 - Gi/o: ↓AC = ↓cAMP = ↓NA release
b - Gs: AC → cAMP → cardiac muscle contraction and smooth muscle relaxation
What are the 4 dopamine pathways?
Nigrostratal pathway - SN to striatum for movement
Mesolimbic pathway - ventral tegmental area (VTA) to nucleus accumbens of the amygdala and hippocampus for reward pathway
Mesocortical pathway - VTA to frontal cortex for executive function
Tubero-hypophyseal pathway - hypothalamus to pituitary gland to inhibit prolactin release and CTZ to induce vomiting
Which conditions is dopamine invovled in?
Parkinson’s - impaired dopamine
Schizophrenia - hyper dopamine
Addiction
Emesis - high dopamine in CTZ
ADHD
How is dopamine snythesised and regulated?
Tyrosine → DOPA via tyrosine hydroxylase → dopamine via DOPA decarboxylase
D2 receptor on presynaptic for autoregulation
DA transporters removes DA from cleft then degraded by MAO-beta
What are the 2 dopamine receptor families
D1 receptor family: D1 & D5, Gs = ↑PKA = ↑DARPP-32
D2 receptor family: D2,3,4, Gi = ↓PKA
What are the 4 main actions of serotonin and where?
Released from raphe nuclei
cortex = heighten perception
hypothalamus = reduced appetite
amygdala = elevated mood
spinal cord = pain suppression
How is serotonin synthesised and regulated?
Tryptophan → 5HT → serotonin via DOPA decarboxylase
5-HT1D is the autoreceptor
5HT transporter removes serotonin from cleft and broken down by MAO
What are the 4 Acetylcholine pathways and ACh function
Nucleaus basalis to cortex
Sept-hippocampal pathway
Substantial Nigra to thalamus
Straital interneurons in the straitum - motor movement
Memory & learning, rewards, arousal
What are the 2 types of ACh receptors
Nicotinic ion channel receptors - fast ionotropic
Muscarinic - slow G-protein, M1 excitory, M2 presynaptic inhibition, M3 excitatory glandular/smooth muscle
M4,5 not known
How is Ach synthesised and regulated?
Choline + Acetyl-CoA = ACh
Presynaptic nicotinic autoreceptor
Re-taken up via choline carrier, broken down by acetylcholinesterase
Presynaptic toxins (botuinum) stops exocytosis of Ach
Function of histamine?
H1 = arousal, H3 = autoregulator
Function: seep / wake, vomiting
Function of Purines?
Adenosine (A1, A2a/2 b) and ATP (P2x)
Functions: sleep, pain, neuroprotection, addiction, seizrures, ischaemia, anticonvulsant
