Behavioral Neuroscience, lecture on Hypothalmic Gating of Lordosis Behavior
LORDOSIS
IX. Serotonin = 5-HT
A. Synthesis of 5-HT
1. produced in the raphé nuclei and the medulla (MSG): B1-B9
a. raphé and MSG nuclei have numerous subdivisions
with specialized projections
2. precursor: tryptophan (Trp)
a. increasing dietary tryptophan will increase transmitter
i. active uptake into the brain
(1) carrier process open to competition
(2) brain Trp levels are determined by plasma
levels of Trp and other amino acids
b. rate limiting
c. converted by tryptophan hydroxylase (TrH; oxidase)
i. TrH never saturated by Trp
ii. rate limiting of the 2 enzymes
3. 5-HTP (5-hydroxytryptophan)
a. 5-HTP decarboxylase
(= aromatic aa decarboxylase = DOPA decarboxylase)
4. Serotonin (5-HT = 5-hydroxytryptamine)
a. Indoleamine (2 ring structure) with widespread
projections to forebrain, cerebellum and spinal cord
i. widespread influence over arousal, sensory
perception, emotion, & higher cognitive functions
(1) inhibits lordosis
(2) pain suppression, sleeping & circadian rhythms,
thermal regulation, corticosteroid receptivity
b. raphé nuclei are subdivided in to regions with
specific projections and therefore specific functions
c. 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
d. pineal hormone Melatonin also synthesized from 5-HT
B. Reuptake and Degradation
1. (like other transmitters) most is taken back up
by 5-HT transporter
a. 5-HTT direction depends on [5-HT]
i. many antidepressant drugs are 5-HT reuptake
blockers & work via 5-HT1A presynaptically
2. primary metabolite is 5-HIAA (5-hydroxyindoleacetic acid)
a. MAO & aldehyde dehydrogenase
C. Receptors
1. 5-HT1A,5-HT1B,5-HT1D, 5-HT1E, 5-HT1F, 5-HT5A: Gi
a. most often 5-HT is thought of as an inhibitory transmitter
b. 5-HT1A in high density in VMN
i. inhibits Lordosis
(1) by hyperpolarization: opens K+ channels
ii. 5-HT1A in raphe are somatodendritic
autoreceptors and inhibit 5-HT cell firing
and release
iii. 5-HT1A presynaptic = anxiolytic
(1) 5-HT1A postsynaptic = anxiogenic
2. 5-HT2A, 5-HT2B, 5-HT2C, 5-HT2D: Gp
a. 5-HT2A & 5-HT2C are dense in POA
i. stimulates lordosis, by limiting locomotion and courtship
b. 5-HT2 anxiogenic
3. 5-HT3: 5-HT-gated non-selective cation (Na+, K+, Ca++)
channels ® depolarization
a. 4 transmembrane segments
b. gene/protein family with GABA, Glu, Gly & Nicotinic-Rs
4. 5-HT4, 5-HT6, 5-HT7 : Gs
a. LSD is an 5-HT6 & 5-HT7 agonist
b. 5-HT7 also dense in hypothalamus
5. 5-HT5B: found in frogs and mice but not humans