Dopamine neurons (DA)
Dopamine is synthesized via two enzymatic steps involving tryrosine hydroxylase and decarboxylase (Note that dopamine neurons are missing the dopamine β-hydroxylase enzyme that would be required for the synthesis of norepinephrine). Dopamine is then stored in vesicles for release. There are 5 different dopamine receptors subtypes which are grouped into being either dopamine1-like (receptors 1 and 5) or dopamine2-like (receptors 2, 3 and 4). D1 and D5 receptors are excitatory, which means that they stimulate the formation of cAMP by activation of the Gs-protein, whereas the other three receptors are inhibitory (Gi). Dopamine 2-like receptors are considered most important for the pharmacological activity.
Like the other monoamines, dopamine
is metabolized intracellular by monoamine oxidase (MAO) and extracellularly by catechol-O-methyl transferase (COMT). It is important to notice that some dopamine neurons have presynaptic 5-HT2A receptors. When stimulated, the 5-HT2A hetero-receptor inhibits the release of dopamine into the synaptic cleft. When you review the various dopaminergic tracts, pay close attention to which neurons have this activity.
Alterations in dopamine neurotransmission are associated with Parkinson’s diseaseand psychotic disorders (e.g. schizophrenia) and psychotic symptoms in other disorders. Thus, most pharmacological therapy aimed at these disorders attempts to either enhance or reduce dopamine's effects in different areas of the brain.
The source nuclei for dopaminergic neurons are located in the brain stem.
Extra info: The source nuclei come from different areas including the substantia nigra, ventrale tegmentum and hypothalamus.
COMT is the primary mechanism for clearing dopamine from the synapse.
Extra info: The primary mechanism for clearing dopamine from the synapse is reuptake.
There is no negative feedback loop for dopamine.
Extra info: There are two negative feedback loops: one at the axon terminus and the other at the somatodentric end.
5-HT2A receptors play an important role in the modulation of pre-synaptic dopamine release throughout the dopaminergic system.
Extra info: Modulation by presynaptic 5-HT2A receptors is thought to occur only in the mesocortical and nigrastriatal tracts.