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Modelli Malattie Neuro
Modelli Malattie Neuro
to human psychiatric and neurological disorders...
Motor function Motivated Behaviour
DOPAMINE
Sexual Behaviour Learning and Memory
Sensorimotor gating
Parkinson disease
Drug of Abuse
Schizophrenia
DAergic Nigrostriatal and Mesolimbic pathways
DOPAMINE RECEPTORS
D1-LIKE FAMILY D2-LIKE FAMILY
D1R D2R (D2L & D2S)
D5R D3R
D4R
Basal Ganglia network
Some of the signal trasduction
pathways of dopamine receptors
FIRING
Pre-synaptic neuron
Degradation
SYNTHESIS TH DA
P
Tyrosine
MA
D3R Ca2+ D3R
O
L-DOPA
RELEASE
TH G
DA
ATP cAMP release
D2R Gi DA DA G
D2R
D
AC
A
DAT
Synaptic cleft
DA Degradation
D2R D1R
G i AC G s
D2R
D3R Numerous
ATP cAMP
cellular
processes
Post-synaptic neuron PKA
regulation
Model of the dopaminergic synaptic
transmission.
.
The
controversy…
D2R
?
?
D3R
Dopamine D2R exists as
two different isoforms
Targeted disruption of
dopamine D2 receptors
Microdialysis probe
2 mm long
FIRING
Pre-synaptic neuron
Degradation
SYNTHESIS TH DA
P
Tyrosine
MA
D3R Ca2+ D3R
O
L-DOPA
RELEASE
TH G
DA
ATP cAMP release
D2R Gi DA DA G
D2R
D
AC
A
DAT
Synaptic cleft
DA Degradation
D2R D1R
G i AC G s
D2R
D3R Numerous
ATP cAMP
cellular
processes
Post-synaptic neuron PKA
regulation
Model of the dopaminergic synaptic
transmission.
.
The effects of haloperidol and quinpirole on DA
release are suppressed in D2R null mice
250
200
injection
150
100
50
0
40 20 0 20 40 60 80 100 120
TIME (min)
Alterata funzione di autoregolazione nei topi mutanti D2
Cocaine
Amphetamine
Cannabinoids
Alcohol
Opioids
Nicotine
Mesolimbic
pathway
Crucial role in
Rewarding effects
induced by natural
events
behavioural response
to drugs of abuse
DOPAMINE AND DRUG
ABUSE
Microdialysis probe
2 mm long
Effetti comportamentali alterati della cocaina
in topi D2 ko
Effetti di plasticità neuronale indotti dalla
cocaina sono alterati nei topi D2 ko
Effetti di plasticità neuronale indotti dalla
cocaina sono alterati nei topi D2 ko
Conditioned place preference
Camera Protocole :
Camera Protocole :
Dopamine D2S isoform is a key element in regulating DA increase
induced by drugs of abuse
We propose that functional D2Smediated presynaptic functions are
pivotal in the rewarding mechanism underlying addiction.
DAergic Nigrostriatal and Mesolimbic pathways
Mutando geneticamente la
TH………….
Induciamo un
severo modello
animale
parkinsoniano
La terapia genetica come
approccio al Parkinson
Microdialysis probe
2 mm long