chapter 6- seratonin

Tryptophan

Synthesises seratonin

Seratonin full synthesis

Tryptophan → 5-HTP→ 5-HT

Tryptophan → 5-HTP catalyst (Rate limiting step)

TPH

5-HTP→ 5-HT catalyst

AADC

TPH1 and TPH2 forms

TPH1- in gut and pineal gland

TPH2- seratonergic neurons

95% of tryptophan makes ____

Kynurenine

Protein rich meal ____ while carbohydrate rich meal ___

Doesnt increase 5-HT, does increase 5HT

Para-chlorophenylalanine (PCPA)

Selectively blocks 5-HT synthesis by inhibiting TPH

Acute tryptophan deletion

Contains large amounts of all other amino acids (LNAA)

Tryptophan loading

Administration of pure tryptophan

agonists at 5-ht1a

buspirone, ispapiron, 8-OH-DPAT

receptor antagonists

WAY-100635, ketanserin, ritanserin

lesions in animals use these drugs:

5-6 DHT, 5-7 DHT

TPH2 knockout mice show:

reduced body fat and mass, increased mortality

TPH 2 knockout mice behavior

more impulsive, cumpulsive, socially poor communication

agressive behavior shown in

resident intruder test

reactive agression

response to a threat

proactive agression

planned rather then provoked. a tangible benefit

Tryptophan metabolizing to kyriutenine catalyzed by

• IDO in brain and immune system

• TDO in liver

TPH2 kockout mice

5-HT release stimulants

• para-chloroamphetamine

• Fonfluramine (appetite surpressor)

• MDMA

5HT inactivation

• 5-HT transporter SERT used in Reuptake

• Selective seratonin Reuptake inhibitors (SSRI)

  • Example: Prozac

Serotonergic system Anatomy

Found in midline of brainstem

Raphe nucleus

Dorsal raphe nucleus and median raphe nucleus

5-HT1a receptors at

Hippocampus, amygdala and DRN

5-HT1a Autoreceptor mechanism

• reduces cAMP

• Inc