2Farma serotonine

Noadrenergic

~organization & neurotransmission
->NE & EP act through the adrenoreceptors

->noadrenergic system involved in many behavioral functions (arousal, cognition, consolidation of emotional memories…)

 eg memories related to fear-inducing situations

Adrenoreceptors

=adrenergic receptors, =metabotropic receptors α1 & α2 and the β1 & β2 receptors

 -> β receptors enhance cAMP synthesis

 -> α2 receptors inhibit the cAMP formation

 

Agonist to adrenergic receptors: used for various disorders
1. a2 agonist: helps nasal congestion + hypertension + drug withdrawal
2. b2 can treat bronchial congestion (asthma ventilator)

A6 Locus coeruleus

=cluster of noradrenergic neurons (brains main source of NE)

1. Important for mediating effect (mediates arousal effect of norepinephrine)
2. Cognitive enhancing effects are mediated by activation of alpha2 receptors in PFC
3. Memory consolidation requires activation by beta receptors in basal lateral amygdala

 

~additional involvement of peripheral acting on vagus nerves (is how fight/flight gets activated)

5-HT

=5-HydroxyTryptamine, =serotonin (full synthesis p21)

Synthesis:
1. Biosynthesis: tryptophane (food)

2. ->conversed to 5-hyrdoxy-trytophane (via tryptophane hydroxylase)

3. ->serotonin

->trytophan to 5-HT=rate limiting step (synthesis can be stimulated by giving large doses of tryptophan of 5-HT
->eating protein-rich food won’t increase tryptophan/5-HT in brain (low protein, high carb: ↑trytphan)

Serotonin storage & release

1) Transported same way as catecholamines (via VMAT2)

2) Autoreceptors control release in same way as catecholamines:
 1. Terminal autoreceptors directly inhibit 5-HT
 2. Somatodendritic autoreceptors indirectly inhibit release by slowing rate of firing neurons

 

3) After release: rapidly removed by reuptake process
 ->done by protein on nerve terminal (5-HT transporter/SERT

 ~Drug Prozac (/fleuxotine): inhibits 5-HT reuptake (SERT)

    =called selective serotonin reuptake inhibitors (SSRIs)

 

Exp on mouse shows importance of transporters: lack of SERT

 =>physical & behavioral abnormalities

Breakdown of 5-HT

~by MAO-A: ->to 5-HIAA (5-hydroxyindoleacetic acid)

5-HIAA often used as measure of activity of serotonergic neurons (when 5-HT neurons fire more rapidly: they make more 5-HT)

Organization of serotonergic system

=very complex and still not fully understood, uses many diff receptors (mostly metabotroop)

1) 5HT1A-receptor

2) 5HT2A-receptor

5HT1A-receptor

~neuronal inhibition (inhibits cAMP production): sleep, thermoregulation, aggression, anxiety
 1. Agonist: buspirone, LSD (hallucinations, altered thoughts and feelings)
2. Antagonist: ergotamine, yohimbine

5HT2A-receptor

~CNS excitation: 1. ↑intracellular calcium levels, uses 2nd messenger system to increase protein kinase C

 2. learning,
3. anxiety contraction of smooth muscle,
4. vasoconstriction/vasodilation blood platelet aggregative

1) Agonist: LSD

2) Antagonist: mirtazapine, ketanserin, atypical antipsychotics

LSD

=Lysergic acid diethylamide

1) Hallucinogenic (hallucinations, altered thoughts & feelings)
2) 5-HT agonist (stimulates serotonin receptor)
3) Dilated pupils, ↑blood pressure & body temperature

 =>very active brain