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Neurotransmitters and Neuromodulators (Dopamine :warning: (1. Mesolimbicā¦
Neurotransmitters and Neuromodulators
Acetylcholine
:check:
An ester neurotransmitter
Acts on cholinergic pathways-
basal forebrain
G-protein-coupled
muscarinic receptors
M1, M3,M5
Excitatory
Phosphatidylinositol turnover
Increase in intracellular calcium level
M2,M4
Inhibitory
autoreceptors
Ligand-gated ion channel
nicotinic
receptors
Eg: 5- HT3
Rapid
excitatory
signal
Dopamine
:warning:
1. Mesolimbic pathway
Midbrain ventral tegmental area to nucleus accumbens
"Reward centre"
Emotional behaviour
Pleasure
Motivation
2. Mesocortical pathway
Midbrain ventral tegmental area to prefrontal cortex
Dorsolateral
prefrontal cortex
Regulates cognition
Executive functions
Ventromedial
prefrontal cortex
Regulates emotions
3. Nigrostratial
pathway
Regulating movement
Damage in this area leads to Parkinson's disease
Projects from substantia nigra to stiratum
parts of
extrapyramidal
nervous system
4. Tuberoinfundibular
pathway
Projects from hypothalamus to infundibular region
Decrease
prolactin release (as opposed to postpartum - increase prolactin release)
Use of antipsychotics
decrease
activity in this region
Increase in prolactin
Galactorrhoea
Amenorrhoea
Sexual dysfunction
5. Thalamic
pathway
Project from hypothalamus to the thalamus
Sleep
Arousal
No evidence shows involvement in schizophrenia
Receptors
D1,D5
Increase cAMP
Excitatory
D2,D3,D4
Decrease cAMP
Inhibitory
Norepinephrine
:no_entry:
Converted into epinephrine in adrenal medulla by phenylethanolamine N-methyltransferase
Located throughout the
brain stem
, mostly in locus coeruleus in the pons
Axons of these neurons project through cerebral cortex, thalamic nuclei, cerebellum,pons and spinal cord
mood, overall arousal, attention and sexual behaviour
Receptors
- adrenergic
alpha 1 , beta 1, beta 3
Excitatory
alpha 2, beta 2
Inhibitory
Serotonin
(5-hydroxytryptamine, 5HT) :star:
2% in CNS,
98% in periphery
80% in
GI Tract - contractility and motility
15-18% in mast cells and platelets (aggregation and blood clotting)
Cannot cross BBB
Synthesised from tryptophan
Midline raphe nuclei of brainstem
Upper
raphe nuclei - send ascending axons throughout the
brain
Caudal
raphe nuclei - send axons to
medulla, cerebellum and spinal cord
Sleep pattern, mood, appetite, pain, pleasure, sexual behaviour, motivation, anxiety
7 types of
receptors
5-HT1 to 7
5-HT1A is the most intensively studied one
Histamine
:<3:
Produced from
histidine
, catalysed by L-histidine decarboxylase
peripheral administration of histidine elevates histamine levels in brain
Can cross BBB
Tuberomammiillary nucleus pathway
Ventral
ascending projection to
hypothalamus
Dorsal
ascending projections to t
halamus, hippocampus, and amygdala
Arousal, wakefulness, feeding behaviour and neuroendocrine responsiveness
Receptors
H1
Excitatory
Increase intracellular calcium level and cAMP level
Smooth muscle,endothelial cell, CNS
H2
Gastric parietal cell,cardiac muscle(heart), mast cells, CNS
Excitatory
Increase in cAMP level
H3
CNS: presynaptic , myenteric plexus
Inhibitory
Decrease in cAMP level
H4
Cells of haematopoietic origin
Mixed - Decrease in cAMP but increase in intracellular calcium level
GABA
:red_flag:
Synthesised from glutamate
GABA-A
receptors :red_flag:
Suubstances such as benzodiazepene facilitate binding of GABA to GABA-A receptors
Increase in intracellular chloride level - leads to
hyperpolarisation
Inhibitory
GABA-B
receptors :red_flag:
Presynaptic
Activation leads to
decrease
in release of GABA
Excitatory
Postsynaptic
Activation leads to more intracellular potassium exit from the cell - leads to
hyperpolarisation
Inhibitory
Deficiency of GABA
Anxiety and depression
General uneasy feeling
Can't sit still for long periods of time
Glutamate
:checkered_flag:
Synaptic plasticity, excitotoxcity,pain perception and long term potentiation
Synthesised from glutamine
Will be recycled back into glutamine in glial cells via glutamine synthetase after action
N-methyl-D-aspartate
receptor (NMDA)
An ion channel which allow entry of cations (Na+, Ca2+) into cells when glutamate binds to it
Leads to
depolarisation
Glutamate is an
excitatory
neurotransimitter
Glycine
:fire:
Synthesised from serine
It is an
inhibitory
neurotransmitter
by increasing intracellular chloride ions level - leads to
hyperpolarisation
Receptors are primarily found in ventral part of the
spinal cord
Ionotropic channel that acts through chloride ion
Peptides
:pencil2:
No reuptake
after action - go through
enzymatic degradation
Co-released with other neurotransmitters - serves as
neuromodulators
Endogenous opioids
:pencil2:
Enkephalin
Opiates receptors
Ī¼ (mu)
šæ (delta)
Ļ° (kappa)
Analgesia, inhibits defensive response
Naloxone
- reverse opiate intoxication
Lipids
:lock:
endocannabioids
CB1 and CB2
receptors
Both are metabotropic - G-protein coupled
CB1 - in brain
CB2 - outside brain
Nucleoside
:beer_mugs:
Adenosine
Neuromodulator
Receptors are G-protein coupled and also coupled to potassium channels
Caffeine
can black adenosine receptors
Souble gases
:!!:
Nitric Oxide (NO)
Produced by endothelial cell - use between cell communication
Triggers secondary messengers
Stimulate
cGMP
Control smooth muscles in intestine
Vasodilation
Produce penile erection
After
glutamate
binds with NMDA, calcium ions enter and bind to calmodulin activating
nitric oxide synthetase
(NOS)
Formation of NO and citruline from
L-arginine
To exert action
Diffuse out to pesynaptic terminal to prolong effect
Diffuse into adjacent neuron and glial cells
to stimulate cGMP