Stahl's - Dopamine Synthesis and Pathways

Question 1

What two enzymes are responsible for converting the amino acid, tyrosine, into DA?

Answer 1

1. Tyrosine hydroxylase (TOH)
2. DOPA decarboxylase (DDC)

Question 2

What happens to excess DA that escapes storage in synaptic vesicles?

Answer 2

They are destroyed within the neuron by monoamine oxidase A&B (MOA-A and MOA-B)

Question 3

What is the transporter that carries newly synthesized DA to synaptic vesicles for storage?

Answer 3

Vesicular monoamine transporter 2 (VMAT2)

Question 4

By what mechanisms is DA inactivated at the synaptic cleft?

Answer 4

1. In striatum and other brain regions, dopamine neurons have a presynaptic transporter, Dopamine transporter (DAT), which whisks DA out of synapse and back into presynaptic terminal for reuse
2. Secondary inactivation extracellularly by catechol-O-methyltransferase (COMT) [primarily in areas where there are no DATs present (e.g. prefrontal cortex)]

Question 5

What are the two groups of dopamine receptor subtypes?

Answer 5

D1-like receptors and D2-like receptors

Question 6

What are the D1-like receptors and their characteristics?

Answer 6

D1 and D5; Excitatory receptors and positively linked to adenylate cyclase

Question 7

What are the D2-like receptors and their characteristics?

Answer 7

D2, D3, and D4; Inhibitory receptors and negatively linked to adenylate cyclase

Question 8

Which dopamine receptors can be found on the presynaptic neuron?

Answer 8

D2 and D3

Question 9

What is the purpose of presynaptic DA receptors?

Answer 9

As both D2 and D3 are inhibitory, they act as autoreceptors to inhibit further release of DA; D3 is more sensitive to DA than D2, therefore it takes a lesser concentration of synaptic DA to activate it to shut off further DA release

Question 10

What are the five classical DA pathways in the brain?

Answer 10

1. Tuberoinfundibular pathway
2. Thalamic pathway
3. Nigrostriatal pathway
4. Mesocortical pathway
5. Mesolimbic pathway

Question 11

Inhibition of prolactin release occurs in which DA pathway?

Answer 11

Tuberoinfundibular pathway

Question 12

Which DA pathway is responsible for motor movements via its connections with the thalamus and cortex?

Answer 12

Nigrostriatal pathway - responsible for extrapyramidal symptoms/SEs

Question 13

Where is the tuberoinfundibular pathway located?

Answer 13

Projects from hypothalamus to anterior pituitary gland

Question 14

Which DA pathway is thought to be involved in sleep and arousal mechanisms?

Answer 14

Thalamic pathway

Question 15

Where is the nigrostriatal pathway located?

Answer 15

Projects from DA cell bodies in brainstem substantia nigra via axons terminating in the striatum (hence nigro-striatal)

Question 16

What is caused by insufficient DA in the nigrostriatal pathway? Excess DA?

Answer 16

Hypokinetic movement disorders such as Parkinson’s Disease characterized by rigidity, akinesia/bradykinesia, and tremor.

Excess DA is thought to underlie hyperkinetic movement disorders such as tics

Question 17

Where is the mesolimbic DA pathway located?

Answer 17

Projects from cell bodies in ventral tegmental area (VTA) of brainstem to nucleus accumbens in ventral striatum, which is part of the limbic system

Question 18

DA release from which pathway is thought to play role in normal emotional behaviors, including motivation, pleasure, and reward?

Answer 18

Mesolimbic pathway

Question 19

Excess DA in this pathway is thought to cause positive symptoms of psychosis and artificial reward of substance abuse.

Answer 19

Mesolimbic pathway

Question 19

DA deficiencies in this pathway hypothetically cause symptoms such as anhedonia, apathy, and lack of energy.

Answer 19

Mesolimbic pathway