Serotonin References

Cross references:   Serotonin (5-HT)     Serotonin Receptors       5-HIAA
Serotonin Transporter      Dopamine (DA)     Dopamine Receptors     Cortisol    

Serotonin Detection       Corticotropin-releasing hormone (CRH)     
CRH Receptors     Arginine Vasopressin     Nucleus Accumbens Septi
Ventral Tegmental Area      Direct Serotonin Pathway     
Indirect Serotonin Pathway      Direct vs. Indirect 5-HT

The bio-active compound most central to this website is 
Serotonin .  This physiologically active compound has been the focus of much research and many scientific papers.  The list of specific topics, below, is an attempt to make the large volume of information that is available more accessible.       

General References       

"Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. ... It is a well-known contributor to feelings of well-being; therefore it is also known as a "happiness hormone" despite not being a hormone."  

Serotonin Detection      

    "5-Hydroxyindoleacetic acid (5-HIAA) is the main metabolite of serotonin in the human body.
Low levels of 5-HIAA in the cerebrospinal fluid have been associated with aggressive behavior and suicide by violent means, correlating with diminished serotonin levels.[1]"    

Serotonin Receptors    
" With the exception of the 5-HT3 receptor, a ligand gated ion channel, all other 5-HT receptors are G protein coupled seven transmembrane receptors that activate an intracellular second messenger cascade to produce an excitatory or inhibitory response.

Serotonin Gate (5-HT3R)    
"The 5-HT3 receptor consists of 5 subunits arranged around a central ion conducting pore, which is permeable to sodium, potassium, and calcium ions. Binding of the neurotransmitter 5-hydroxytryptamine (serotonin) to the
5-HT3 receptor opens the channel, which, in turn, leads to an excitatory response in neurons."   

Serotonin Metabotropic Receptor
    "They are indirectly linked with ion-channels on the plasma membrane of the cell through signal transduction mechanisms, often G proteins. Hence, they are a type of G protein-coupled receptor."    

G-Protein Coupled Receptors
"G protein-coupled receptors (GPCRs) ... comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal transduction pathways and, ultimately, cellular responses."

Serotonin Receptor Evolution  
"Evolutionarily, serotonin existed in plants even before the appearance of animals. Indeed, serotonin may be tied to the evolution of life itself, particularly through the role of tryptophan, its precursor molecule."   

Serotonin Transporter  or  SERT    
    "The serotonin transporter (SERT) is a monoamine transporter protein. This is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it in a sodium-dependent manner."

Direct Serotonin Pathway   
The  Dorsal Raphe Nucleus (DRN) is one of the sites at which Serotonin turnover is modulated.  Members of the  Corticotropin-releasing factor family influence the level of  Serotonin in the brain by modulating the activity of serotonergic neurons in the caudal portion of the DRN .   

Indirect Serotonin Pathway    
    The "Indirect Serotonin Pathway" has two sequential parts.  In the first part of the sequence, Cortisol reduces the sensitivity of Testosterone   Receptors to Luteinizing Hormone .  In the second part of the sequence, Testosterone decreases the sensitivity of Serotonin Receptors .    

Direct vs. Indirect 5-HT
Direct Serotonin Pathway  modulates the amount of Serotonin present at the  Serotonin Receptors .  The Indirect Serotonin Pathway modulates the sensitivity of the Serotonin Receptors  to however much  Serotonin is present. 

Amphioxus References   

Amphioxus Serotonin System    

    "Serotonin immunoreactivity was confined to the central nervous system (CNS) and digestive tract in adult specimens of B. floridae."   
    "...we found orthologs to three serotonin receptors, namely 1, 5 and 6..." 

Reverse Engineering Amphioxus Serotonin   
This section resulted from an attempt to justify the assumption that the 5-HT3R is present in the amphioxus.   However, I did an exhaustive search for evidence of the 5-HT3 receptor in amphioxus and found nothing specifically about 5-HT3R in anything below the mammals on the evolutionary scale. 

Lamprey References   

Lamprey Serotonin System
    "The results reveal strong resemblances between lampreys and other vertebrates in the spatio-temporal pattern of development of brainstem populations. This study also reveals a shared pattern of early ascending and descending serotonergic pathways in lampreys and jawed vertebrates." 

Comparing Amphioxus and Lamprey Serotonin   
     5-HT3R has not been reported in either the amphioxus or the lamprey.       

Teleost References   

Teleost Serotonin   

Rodent References   

Rodent 5-HT1R   
    "Studies using 5-HT1A and 5-HT1B receptor agonists show an effective reduction in aggressive behavior."   
    Increased 5-HT at the autoreceptors in the DRN reduces the effect the serotonergic neurons have on their target neurons while increased 5-HT at the postsynaptic receptors, which are on the target neurons, increases the effect of the serotonergic neurons on their target neurons.   

Rodent 5-HT3R   
    "Between 70 and 95% of the 5-HT3R-expressing cells were GABAergic throughout the telencephalon." 
Overall, these results support an important role of 5-HT in the control of the excitability of apical dendrites of pyramidal neurons in the medial PFC through the activation of 5-HT3 receptors in GABAergic interneurons.

Rodent Serotonin & Aggression
    "Serotonin-depleting lesions of midbrain raphe ... induced intraspecific agressiveness in grouped Wistar male rats but failed to increase mouse-killing behaviour."  

Rodent Glucocorticoid-Serotonin Interaction   
 During the rat exposure period, control mice ... showed a profound rise in free corticosterone levels. In contrast,
GR-impaired (GR-i) (transgenic) mice displayed ... no increase of free corticosterone.   

Rodent Testosterone 5-HT Interaction    
    These references specify three serotonin receptors that seem to be downregulated by testosterone.  The three are: 5-HT1AR, 5-HT2AR and 5-HT3R.    

Rodent Testosterone 5-HT Interaction    
    " steroids inhibited the effect of serotonin at the 5-HT3 receptor."    

Rodent AVP, 5-HT and Aggression   
    "Animal studies show that arginine vasopressin facilitates aggression, while serotonin (5-HT) inhibits aggression by blocking the activity of the vasopressin system."  

CRH & Serotonin  
        These results suggest that the opposing effects of dorsal raphé CRF on 5-HT release in the nucleus accumbens are dependent on differential activation of CRF1 and CRF2 receptors in the dorsal raphé nucleus.  

Cortisol & Testosterone & Serotonin  
        "Elevated Cortisol , and the resulting lowered Testosterone , are accompanied by an increase in Serotonin (5-HT) activity, as indicated by an elevated 5-HIAA / 5-HT ratio because both are parts of the  Stress response."   

Primate References   

Primate Serotonin
    "These findings suggest that low Cerebrospinal Fluid  5-HIAA concentrations quantified early in life is a powerful biological predictor of future excessive aggression, risk taking, and premature death among nonhuman primate males."  

Human References   

Human Serotonin   
    "Decreases in serotonin transmission seem to be associated with the increased performance of behaviors that are usually suppressed

Serotonin & Impulsivity    

    Reduced overall central 5-HT function in the Limbic - Hypothalamic system is associated with suicidal and/or impulsive aggressive behaviors

Criminal Serotonin      
    "Recidivists who committed a new violent offense or arson had significantly lower Cerebrospinal Fluid 5-hydroxyindoleacetic acid ( 5-HIAA ) and homovanillic acid ( HVA ) concentrations and blood Glucose nadirs after oral glucose challenge than did nonrecidivists."  
   "Pharmacological challenges pinpoint 5-HT(1A) and 5-HT(1B) receptors as key players in the modulation of offensive aggression."      

Criminal Testosterone & Serotonin   
    "The Serotonin function was inversely correlated more strongly with Impulsivity than with Aggression . Plasma Testosterone correlated positively with aggressive acts."    

Criminal Testosterone, Serotonin & ACTH     
    "Alcoholic, impulsive offenders with antisocial personality disorder had low mean  Cerebrospinal Fluid (CSF) 5-hydroxyindoleaceticacid ( 5-HIAA ) and corticotropin ( ACTH ) levels and high mean CSF Testosterone concentrations.

Criminal Vasopressin & Serotonin      
    "Central Arginine Vasopressin may play a role in enhancing, while Serotonin plays a role in inhibiting, aggressive behavior in personality-disordered individuals. 

Serotonin & Dominance    
    "The brain serotonergic system appears to inhibit aggression and spontaneous locomotor activity in both fish and mammals."   
    "By contrast, the brain dopaminergic system appears to stimulate aggressive behaviour in both fish and mammals, and dominant fish show signs of elevated dopaminergic activity in telencephalon."  

Accumbal 5-HT Receptors     
    "Experimental investigation has identified the following Serotonin Receptors as playing a role in the modulation of Dopamine in the Nucleus Accumbens Septi :  5-HT1A, 5-HT1B, 5-HT(1B/1D),  5-HT2A, 5-HT2B, 5-HT2B/2C, 5-HT2C/2B, 5-HT2C, 5-HT3, 5-HT4."   

Serotonin & Dopamine    
    "These results indicate that 5-HT2A but not 5-HT(2B/2C) receptors participate in the facilitatory control exerted by endogenous 5-HT on accumbal DA release. Conversely, 5-HT(2B/2C) receptors tonically inhibit basal DA release in both brain regions."  

Book: 5-HT DA Interaction: Chap 1: CNS     
    "Several 5-HT receptor subtypes, including the 5-HT(1A), 5-HT(1B), 5-HT(2A), 5-HT(3) and 5-HT(4) receptors, act to facilitate DA release, while the 5-HT(2C) receptor mediates an inhibitory effect of 5-HT on DA release."  
    "In spite of a direct effect of 5-HT by its receptors located on DA cells, 5-HT can modulate their activity indirectly, modifying gamma-amino-n-butyric acid (GABA)-ergic and glutamatergic input to the VTA and SNc."  

Cortisol & Serotonin  
     It's difficult to draw solid conclusions from impairing the function of such a wide-spread element of the hormonal system as the Glucocorticoid Receptor   
    I'm biased, since the report's conclusions don't support my hypothesis, but, that being said, I don't think any definite conclusions can be drawn from this study.  

    Dopamine Receptors     
    Nucleus Accumbens Septi          
    Ventral Tegmental Area              

Serotonin References
121218 - 0111 (modified)