- The presynaptic cell (sending cell) makes serotonin (5-hydroxytryptamine, 5HT) from the amino acid tryptophan and packages it in vesicles in its end terminals.
- An electrochemical nerve signal passes down the presynaptic cell into its end terminals.
- The nerve signal stimulates the vesicles containing serotonin to fuse with the cell membrane and dump serotonin into the synaptic cleft.
- Serotonin passes across the synaptic cleft, binds with special proteins called receptors on the membrane of the postsynaptic cell (receiving cell) and sets up a new electrochemical signal in that cell (the signal can stimulate or inhibit the postsynaptic cell). Serotonin fits with its receptor like a lock and key.
- The remaining serotonin molecules in the cleft and those released by the receptors after use get destroyed by enzymes in the cleft (monoamine oxidase (MAO) and catechol-o-methyl transferase (COMT)). Some get taken up by specific transporters on the presynaptic cell (reuptake). In the presynaptic cell, the absorbed serotonin molecules get destroyed by MAO and COMT. This enables the nerve signal to be turned "off."
A similar process occurs for norepinephrine, which is also implicated in mood, emotions and MDD. Serotonin, norepinephrine and dopamine are chemically similar and belong to a class of neurotransmitters called monoamine neurotransmitters. Because these chemicals are structurally similar, they are all recognized by the enzymes MAO and COMT.
Now let's look at how antidepressants work.