Dopamine

Question 1

History

Answer 1

Synthesized in 1910 by George Barger and James Ewens.

Its role as a neurotransmitter was discovered in 1958 by Arvid Carlsson (awarded the Nobel Prize)

Question 2

Synthesis

Answer 2

The first step in the synthesis of dopamine is tyrosine, which is an amino acid found in dietary proteins. Tyrosine is taken up from the blood into neurons where it is converted to L-DOPA (dihydroxyphenylalanine) by the enzyme tyrosine hydroxylase. L-DOPA is then converted to dopamine by dopa decarboxylase.

Question 3

Storage

Answer 3

Dopaminergic neurons originate in substantia nigra pars compacta, ventral tegmental area (VTA), and hypothalamus. These project axons to large areas of the brain through four major pathways:

The mesolimbic pathway
The mesocortical pathway
The nigrostriatal pathway
The tuberoinfundibular pathway

Question 4

The mesolimbic pathway

Answer 4

The mesolimbic pathway transports dopamine from the (VTA) ventral tegmental area (in the midbrain) to the nucleus accumbens (found at the junction of the caudate and putamen). This is a reward pathway. Blockage of D-2 receptors in this pathway is thought to account for the therapeutic benefit of antipsychotics.

Question 5

The mesocortical pathway

Answer 5

The mesocortical pathway goes from the VTA to the frontal cortex. This pathway is involved with motivation and emotion. Blockage of D-2 receptors in this pathway is thought to lead to the negative symptoms of schizophrenia.

Question 6

The nigrostriatal pathway

Answer 6

The nigrostriatal pathway connects the substantia nigra to the striatum (caudate and putamen). Blockage here produces extra pyramidal side effects (EPSE’s).

Question 7

The tuberoinfundibular pathway

Answer 7

The tuberoinfundibular pathway goes from the hypothalamus to the pituitary gland. Blockage of dopamine in this pathway causes the pituitary gland to secrete prolactin.

Question 8

Breakdown

Answer 8

Dopamine is broken down by catechol-O-methyl transferase (COMT) into 3-Methoxytyramine and by monoamine oxidase (MAO) into 3,4-Dihydroxyphenyl-acetic acid. It is metabolised by both forms of MAO (MAO-A and MAO-B).

Question 9

Receptors

Answer 9

Dopamine receptors are a class of metabotropic G protein-coupled receptors

There are five receptor subtypes D1, D2, D3, D4, and D5.

D1 and D5 are referred to as D1 like receptors. Activation of this family of receptors activates adenylyl cyclase (aka adenylate cyclase), increasing the intracellular concentration of the second messenger cyclic adenosine monophosphate (cAMP).

D2, D3, and D4 are referred to as D2 like receptors. Activation of this family of receptors inhibits the formation of cAMP by inhibiting the enzyme adenylyl cyclase.