Serotonin (also known as 5-HT) is also a monoamine neurotransmitter. It's thought to contribute to feelings of happiness and wellbeing.

Neurons that express serotonin are primarily located in the raphe nuclei (which are distribute across the entire brainstem - midbrain to medulla). Axons then distribute these across the entire brain, with axons in the lower raphe nuclei terminating in the cerebellum and spinal cord, and higher up ones terminating throughout the cortex and sub cortex (leading to serotonin also having a neuromodulatory affect on the whole brain function).

We have already seen that the suprachiasmatic nucleus in the hypothalamus induced sleep by inhibiting the function of the serotonin neurons in the raphe nuclei (part of the ascending activation system).



Serotonin produces both excitatory and inhibitory (depolarization and hyperpolarization, respectively) effects depending upon the receptor target it binds to.

The number of compounds that can inhibit serotonin reuptake (ecstasy, cocaine, anti-depressants), or act as agonist on serotonin receptors (mescaline, LSD, magic mushrooms), implies an association between increased serotonin and increased mood.


There are three main types of antidepressants, all of which increase the action of serotonin on the post-synaptic membrane:

  • Monoamine oxidase inhibitors; these block the breakdown of 5-HT by the enzyme monoamine oxidase.
  • Tricyclics; these block the 5-HT reuptake pump, but have a broad range of effects on many other receptors (a so called ‘dirty drug’), producing multiple adverse side effects.
  • Selective serotonin reuptake inhibitors; these have a ‘cleaner’ pharmacological profile in blocking 5-HT reuptake so produce a therapeutic effect without the side effects.

Effect on Mood

The effect of antidepressants on synaptic transmission are immediate, whereas the therapeutic (mood) effect on depression commonly takes several weeks. To explain this discrepancy, theories have described long term changes in the neural responses to antidepressants which bring about the therapeutic effect.

Following long-term administration of the antidepressant, the autoreceptors on the soma are desensitized (decreased in number), which allows a recovered increase in the firing rate of 5-HT neurons and of 5-HT release. Hence since there are more molecules in the synapse, and only the autoreceptors have had their sensitivity altered, the postsynaptic receptors receive a stronger transmission.