Norepinephrine neurons (NE)
Norepinephrine is synthesized via three enzymatic steps involving tryrosine hydroxylase, decarboxylase and dopamine β-hydroxylase. It is then stored in vesicles at the axonal end for release. There are 9 different norepinephrine receptors subtypes identified. This slide shows the major postsynaptic and presynaptic α- and β- receptors. Norepinephrine is metabolized intra-cellularly by monoamine oxidase (MAO) and extra-cellularly by catechol-O-methyl transferase (COMT).
Some of the earliest links between biological factors and psychiatric disorders were shown to correlate with catecholamine
dysregulation. Pheochromocytomas were often accompanied by the symptoms of anxiety, and it was know that anxiety produced systemic symptoms which could be minimized with the use of beta receptor antagonists. Currently, the monoamine theory of depression is based on the dysregulation of both norepinephrine and serotonin. In the case of depression, the evidence includes altered CSF levels of metabolites of NE and 5-HT, drugs which deplete brain NE and 5-HT often cause depressive symptoms, and antidepressant drugs appear to increase activity of brain NE and/or 5-HT.
In the absence of DA β-hydroxylase, a norepinephrine neuron becomes a dopamine neuron.
A dysregulation of norepinephrine is associated with depression.
Extra info: According to the monoamine hypothesis, depression is caused by a dysregulation of norephinephrine and serotonin.
Noradrenergic α2 auto-receptors are present on the presynaptic axon providing a quick negative feedback loop in the synapse.
Extra info: This sort of auto-receptor provides the synapse with a quick mechanism for inhibiting futher release of norepinephrine into the synapse.
α2 auto-receptors decrease post-synaptic α1 neurotransmission but NOT β1- and 2- neurotransmission.
Extra info: The α2-receptors decrease the transmission of norepinephrine, which freely interacts with both α and β-receptors.