Serotonin

Serotonin

The monoamine neurotransmitter that is synthesized from tryptophan. It plays a crucial role in regulating mood, emotions, sleep, and appetite.

Tryptophan hydroxylase (TPH)

The enzyme that catalyzes the first and rate-limiting step in serotonin biosynthesis by converting tryptophan to 5-hydroxytryptophan (5-HTP).

Aromatic amino acid decarboxylase (AADC)

The enzyme that is responsible for the final step in serotonin biosynthesis by converting 5-HTP to serotonin (5-HT).

Enchancing Serotonin Synthesis

Serotonin can be stimulated by giving a large dose of tryptophan or 5-HTP. A low protein, high carbohydrate diet increases serotonin synthesis by stimulating insulin release which removes competing LNAAs from the bloodstream. Tryptophan loading can cause increases in mood and cognition.

Large neutral amino acids (LNAAs)

The group of amino acids that share similar chemical properties and compete for transport across the blood-brain barrier with tryptophan. The ratio of tryptophan to competitors determines the rate of serotonin synthesis.

Depleting Serotonin Sythesis

Serotonin can be depleted by feeding large amounts of non-tryptophan LNAAs or a high protein, low carbohydrate diet. Tryptophan depletion can cause a relapse of depression and disrupt memory and attention.

Vesicular Monoamine Transporter 2 (VMAT2)

The protein responsible for packaging and transporting serotonin into synaptic vesicles within neurons.

Regulation of Serotonin Release

Terminal autoreceptors directly inhibit 5-HT release. Somatodendritic autoreceptors indirectly inhibit release by slowing the rate of neuron firing.

5-HT transporter (SERT)

The protein responsible for uptake of serotonin from the synaptic cleft back into the presynaptic neuron.

MAO-A

The enzyme responsible for breaking down serotonin into the metabolite 5-hydroxyindoleacetic (5-HIAA)

Raphe nuclei

The collection of serotonergic neurons that are located in the midline of the brainstem.

5-HT-_1A receptors

The serotonin somatodendritic autoreceptors concentrated in the hippocampus, amygdala, and dorsal raphe nucleus that reduce cAMP synthesis by inhibiting adenylyl cyclase and increase the opening of K⁺ channels that hyperpolarize the membrane.

5-HT-_2A receptors

The serotonin metabotropic receptors found in the cortex that activate phosphoinositide second-messenger systems that increase Ca²⁺ levels in postsynaptic cells and activate protein kinase C.

3,4-methylenedioxymethamphetamine (MDMA)

The drug responsible for increasing serotonin release by reversing the serotonin transporter (SERT). In high doses, this drug can lead to persistent serotonergic loss but in lower doses has been used to treat PTSD.

Serotonin reuptake inhibitors (SSRIs)

The class of drugs responsible for increasing serotonin release by blocking serotonin transporter activity and preventing reuptake.

ex) Fluoxetine (Prozac)

5-HT_1A receptor agonists

The drugs that activate 5-HT_1A receptors and play a role in regulating mood and anxiety.

ex) Buspirone, Ipsapirone, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT)

5-HT_2A receptor agonists

The drugs that activate 5-HT_2A receptors and play a role in cogniton, perception, and mood.

ex) Lysergic acid diethylamide (LSD), 1-(2,5-dimethoxy-4-iodophenyl)-2-amino propane (DOI); hallucinogens

5-HT_2A receptor antagonists

The drugs that block 5-HT_2A receptors and D₂ receptors that are used to treat shcizophrenia

ex) Clozapine (clozaril), risperidone (risperdal)