Behavioral Neuroscience, lecture on Afferent Path and SCN
BIOLOGICAL RHYTHMS
IX. Serotonin, 5-HydroxyTryptamine (5-HT)
A. Synthesis of Indoleamines (2 ring structure)
1. precursor: tryptophan (Trp)
a. increasing dietary Trp will increase transmitter
i. active uptake into the brain
(1) carrier process open to competition
(2) brain Trp levels are determined by plasma
ratio of Trp to other amino acids
b. rate limiting
c. converted by tryptophan hydroxylase (TpH; oxidase)
i. TpH never saturated by Trp
ii. rate limiting of the 2 enzymes
ii. requires O2
2. 5-HTP (5-hydroxytryptophan)
a. 5-HTP decarboxylase
(= aromatic aa decarboxylase = DOPA decarboxylase)
3. Serotonin (5-HT = 5-hydroxytryptamine)
a. usual output for indoleaminergic neuronal cells, but
b. converted by N-acetyltransferase +
hydroxyindole-O-methyltransferase (HIOMT)
4. Melatonin is synthesized from 5-HT
a. a hormone made in the pineal
5. Histamine is made from histadine by histidine decarboxylase
(similar to aaad)
B. Reuptake and Degradation
1. (like other transmitters) most is taken back up
by 5-HT transporter = 5-HTT
a. transport direction depends on [5-HT]
b. from transporter gene family; including transporters for
NE, DA, GABA and glycine
i. transporter genes are regulated by hormones
c. 5-HTT allele length influences human affective disoders (depression)
2. most antidepressants (like prozac or zoloft) are SSRIs selective serotonin reuptake inhibitors
3. primary metabolite is 5-HIAA (5-hydroxyindoleacetic acid)
a. MAO & aldehyde dehydrogenase
C. Receptors (17 types)
1. 5-HT1A,5-HT1B,5-HT1D, 5-HT1E, 5-HT1F, 5-HT1P, 5-HT1S: Gi ®X cAMP
a. most often 5-HT is thought of as an inhibitory transmitter
b. also inhibits by hyperpolarization: opens K+ channels
ii. 5-HT1A in raphe are somatodendritic
autoreceptors and inhibit 5-HT cell firing
and release
2. 5-HT2A, 5-HT2B, 5-HT2C, 5-HT2D: Gp ® ÝPLC ® ÝIP3/DG® ÝCa++/PKC
3. 5-HT3: 5-HT-gated non-selective cation (Na+, K+, Ca++)
channels ® hyperpolarization or depolarization
a. 4 transmembrane subunits
b. gene/protein family with GABA, Glu, Gly & Nicotinic-Rs
4. 5-HT4, 5-HT6, 5-HT7 : Gs® ÝcAMP
5. 5-HT5A:Gi ® ¯ AC and
Gp ® Ý IP3 ® Ca++
5-HT5B: G?
D. 5-HT is produced in the vertebrate raphé nuclei and the medulla (MSG): B1-B9
1. median raphé innervates SCN core
2. project to forebrain, cerebellum and spinal cord
(also found peripherally- especially blood platelets and intestine of almost every animal species;
also venom of amphibians, wasps, scorpions, sea anemone; also octopus salivary glands,
pineapples and bananas)
a. distribution pattern pattern is widespread
3. widespread influence over arousal, sensory perception,
emotion, & higher cognitive functions
a. pain suppression, sleeping & circadian rhythms,
thermal regulation, corticosteroid receptivity
i. LSD blocks some 5-HT receptors,
stimulates 5-HT5A, 5-HT6 & 5-HT7 and inhibits raphe cells
b. 5-HT1A presynaptic = anxiolytic
i. 5-HT1A postsynaptic = anxiogenic
(1)5-HT1A in high density in raphe & hippocampus
(a) 5-HT1B,5-HT1D in substantia nigra
ii. 5-HT2 anxiogenic
(1)5-HT2A & 5-HT2D are dense in hippocampus
iii. 5-HT4 in dense in hippocampus,
5-HT7 dense in thalamus, hypothalamus & amygdala
4. Many Invertebrate Neurons are also Serotonergic
a. Aplysia: 5-HT interneurons
b. Leech: Large Retzius cells
