Chapter 6: Serotonin Flashcards
How is serotonin synthesized?
From the amino acid tryptophan which comes from dietary protein. The enzyme tryptophan hydroxylase converts tryptophan to 5-HTP. Then the enzyme aromatic L-amino acid decarboxylase (AADC) converts 5-HTP to sertonin (5-HT).
How can serotonin be inactivated?
There are two ways:
- reuptake by the 5-HT transporter protein (SERT)
- metabolism by the enzyme MAO-A. The breakdown product is 5-HIAA.
Describe the anatomy of serotonergic pathways.
Most of the serotonergic neurons in the central nervous system originate from the raphe nuclei in the brainstem. The raphe nuclei send serotonergic fibres to most of the regions in the forebrain.
How is serotonin associated with obesity?
It helps regulate appetite and energy metabolism by acting on the hypothalamus. Some serotonin receptor agonists and antagonists reduce appetite and food intake. Some agonists are currently prescribed for the treatment of obesity.
What are the two main serotonergic receptor subtypes?
- 5-HT1A receptors
2. 5-HT2A receptors
How do 5-HT1A receptors work?
The 5-HT1A receptors work through two mechanisms:
1) inhibiting adenylyl cyclase which reduces cAMP synthesis
2) increasing the opening of potassium (K+) channels and increasing membrane hyperpolarization which decreases cell firing
Where are 5-HT1A receptors located?
5-HT1A receptors are found in many parts of the brain but they are especially concentrated in the hippocampus, septal area, amygdala, and dorsal raphe nucleus.
5-HT1A receptors also function as somatodendritic receptors in the dorsal and median raphe nuclei.
How do the 5-HT2A receptors work?
The 5-HT2A receptors work by activating the phosphoinositide second-messenger system which increases calcium (Ca+2) levels in the postsynaptic cell and activates protein kinase C.
Where are 5-HT2A receptors located?
5-HT2A receptors are also found in many parts of the brain (e.g. neocortex, striatum, nucleus accumbens) but are especially concentrated in the cerebral cortex.
What is the rate-limiting part of serotonin synthesis?
Tryptophan availability limits serotonin synthesis (step 1). Tryptophan enters the brain from the bloodstream and this entry is determined by the plasma ratio of tryptophan to other large neutral amino acids (LNAAs) that compete for transport across the blood-brain barrier.
How can serotonin synthesis be increased?
- direct tryptophan administration (tryptophan loading)
- comsumption of proteins with very high tryptophan content
- consumption of a high-carbohydrate, low-protein meal
How can serotonin synthesis be reduced?
By tryptophan depletion caused by administration of an amino acid mixture lacking tryptophan.
How do changes in the tryptophan-to-large neutral amino acid (LNAA) ratio affect mood and cognition?
Low to modest increases have no effect on mood or cognition.
Larger increases positively enhance mood and cognition.
Extremely high increases have negative effects on mood and cognition.
Describe the effects of acute tryptophan depletion have on people’s mood.
No effect on healthy people.
Symptom relapse in depressed patients in remission who are being treated with serotonergic antidepressant drugs.
Describe the effects of tryptophan depletion on memory.
It impairs memory consolidation of verbal information.
