Dopaminergic neurotransmission

Question 1

Dopamine

Answer 1

• monoamine NT and hormone
• 5 types of receptors
• produced in substance nigra pars compacta and ventral tegmental area
• role in reward-driven learning
• cannot cross blood-brain barrier

Question 2

Dopamine receptor types

Answer 2

D1 and D5: Gs pathway
D2: Gi pathway
D3 and D4: not known

Question 3

Parkinson’s disease

Answer 3

• age-related degenerative disease
• tremor and motor impairment
• caused by loss of dopamine- secreting neurons in substansia nigra pars compacta
• dopamine as intravenous medication increases HR and BP, but usually L-DOPA is given

Question 4

Dopaminergic pathways: Direct loop

Answer 4

Substansia nigra - D1 receptor in putamen - putamen (inhibitory) - Globus pallidus internus (dissinhibition) - thalamus - cortex
INCREASED CORTICAL ACTIVITY

Question 5

Dopaminergic pathway: Indirect loop

Answer 5

Substansia nigra - D2 receptor in putamen - inhibition of putamen - globus pallidus externus - subthalamic nucleus (exitatory) - Globus pallidus internus (inhibitory) - thalamus - cortex
DECREASED CORTICAL ACTIVITY

Question 6

Dopaminergic pathway: Parkinson’s disease

Answer 6

Dopaminergic neurons degenerated - globus pallidus internus not inhibited - inhibitory to thalamus - cortex
DECREASED CORTICAL ACTIVITY

Question 7

Synthesis od Dopamine

Answer 7

tyrosine - TYROSINE HYDROXYLASE - L-DOPA - DOPA DECARBOXYLASE - dopamine

Question 8

VMAT 1 or 2 transporter

Answer 8

takes up dopamine into vesicles in presynaptic nerve terminal

Question 9

Reserpine

Answer 9

• anti-psychotic and anti-hypertensive drug
• irreversibly blocks VMAT
• long lasting effects

Question 10

Selegiline (Deprenyl)

Answer 10

• MAO-B inhibitor

- used in treatment for early stage Parkinson’s

Question 11

Amantadine

Answer 11

• anti-viral and anti-Parkinson’s drug
• dopaminergic, noradrenergic, serotoninergic substance
• blocks MAO-A and NMDA receptors
• raise beta-endorphin/ beta-lipotropin levels

Question 12

Dopamine metabolism

Answer 12

1. dopamine - MAO-A/B - DOPA-L
2. DOPA-L - Aldehyde dehydrogenase - DOPA-C
3. DOPA-C - COMT - homovanillic acid
4. homovanillic acid excreted into urine

Question 13

Substances that induce Parkinson’s

Answer 13

B-methyl-amino-L-alanine BMAA
MPTP (heroin contaminant)
- taken up by nerve terminals - metabolized by MAO-B to MPP+ the active agent - complex 1 inhibitor

Question 14

Schizophrenia

Answer 14

• increased dopaminergic activity and/or decreased glutamatergic activity
• increased dopamine level in brain
• increased level of homovanillic acid in liquor
• increased number of D2 receptors

Question 15

Carbidopa

Answer 15

• DOPA decarboxylase inhibitor (L-dopa -> dopamine)

- more L-DOPA enters the brain