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Catecholamines
9/4/2015
Catecholamines
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Neurotransmitters
Distribution
Synthesis
Vesicular Storage
Inactivation
Regulation
Release
Chemical structure of biogenic amines
NE in the PNS
Functional Roles of DA in the
CNS
• Mesolimbic: Role in addiction, reward,
mood, dysfunction associated with
mental disorders
• Mesocortical: Role in attention, mood,
decision making, dysfunction associated
with mental disorders
• Nigrostriatal: Role in movement
initiation, dysfunction associated with
Parkinson’s disease
Functional roles for NE in
CNS
LC neurons firing rate
Copyright © 2004 Allyn and Bacon
Vesicular storage of NE
Effects of VMAT2 loss of
function mutation
Role of VMAT2 in DA neurons
Inactivation: Reuptake
Inactivation: Extracellular
degradation
COMT polymorphisms
COMT-15% striatal DA
-60% pre-frontal DA
Chen et al, 2004 AJHG
COMT polymorphisms
• Sex differences in effect of polymorphism
– Females: high DA, lower levels of COMT activity, no effect of
met isoform
– Males: low DA, higher COMT activity, improve with met
isoform
• Idea of optimal DA concentrations, especially in PFC
– Animals lacking COMT have higher DA in prefrontal cortex
• Explain differential susceptibility to DA related illness
– ADHD too little DA (men)
– Depression too much DA (women)
Regulation of CA synthesis
Phosphorylation affects kinetic
properties of TH
Regulation by neural
stimulation
Effect of Electrical Stimulation of LC on TY-OH activity in Hippocampus
TY-OH
Electrical Stimulation
(15 min., 20 Hz, 2 ms pulses)
Contralateral Control
Activity (pmoles/mg/min)
31.6
+ 2.9
7.8 + 0.5
Kinetic Properties of HC TY-OH after LC Stimulation
(X
Stimulated H C
Contralateral HC
Km tyrosine
1 0-6 M)
Ki NE
(X
1 0-3 M)
5 . 4 + 0.7
7.66
+ 0.15
53.6 + 2.1
0.39
+ 0.02
Release of CA
• Ca2+ dependent
exocytosis (DBH
release w LDCV)
• Release at
varicosities
Role of pre-synaptic
autoreceptors
1. Inhibit release by blocking Ca entry
2. Blocks release by inhibiting
synthesis and vesicle uptake
Tonic vs bursting activity
• Tonic firing: single spikes, all DA typically
cleared after the spike
• Burst firing: released DA can
accumulate-amount depends on regional
variations in DAT levels
• D2 autoreceptor antagonists increase
overall firing rate and amount of bursting
Tonic-single spike vs burst in
a spiking VTA DA neuron