Area-1255 Portal 2: Benefits of a 5-HT7 Agonist VS 5-HT7 Antagonist (Better to Activate OR Block 5-HT7 Receptors)

The 5-HT(7) RECEPTOR is a GPCR (G-Protein-Coupled-Receptor) (1) and the Serotonin-Receptor subtype to which Serotonin has highest affinity for (low nanomolar concentrations) (2)..in layman's terms - this means that one could have low serotonin production and this is the receptor that will most likely be most active* even in the presence of very little serotonin.

It displays constitutive activity and thus a variety of ligands can activate it and a plethora of endogenous modulators may attempt to alter it's signaling under certain circumstances (such as STRESS)(3).

It plays a key role in mood, behavior, cognition (flexibility/task switching, organization of thoughts, retention of memories / information). It is specifically affected by (UPREGULATED) by STRESS (4) and , in turn, upregulates GLUCOCORTICOID Receptors (5) which leads to more cortisol activity and affinity afterwards - as such, maintaining abnormally high activity at this receptor can contribute to chronic stress-states and stress-induced deficits in behavioral flexibility which includes social isolation and memory issues in relation to emotional memory and integration (6) (7).

{5-HT7 Receptors also INCREASE with AGE - whereas 5-HT1A's decrease in old Age.}

~MORE ABOUT THE 5-HT7 SEROTONIN RECEPTOR HERE~

THE BENEFITS OF 5-HT7-RECEPTOR AGONISTS INCLUDE

Increasing LTM (Long-Term-Memory) and retention (8) (9).
Increasing Fear-Memory Retrieval (10).
Reducing NMDA-Receptor Expression (only relevant after long-term agonism, short-term is opposite effect) (11)
Reducing Re-Consumption of Alcohol and Thus Alcohol Reinstatement (12).
Treatment of 'Fragile-X-Syndrome' (FXS) and reduction of glutamatergic-tone (13) (14).

EXAMPLES OF A PURCHASABLE 5-HT7-RECEPTOR AGONIST INCLUDE...

AS-19 Purchasable @ TOCRIS BIOSCIENCE

THE BENEFITS OF 5-HT7-RECEPTOR ANTAGONISTS INCLUDE

Rapidly decreasing Depression Symptoms ( )
Increasing Behavioral / Cognitive Flexibility ( )
Reducing Stress-Induced Anhedonia ( )
Increasing Resilience / Stress Adaptation ( )
Increasing Sensitivity to Amphetamine and Blocking the Reduction in Dopamine Induced by Amphetamine ( )

EXAMPLES OF A 5-HT7-RECEPTOR ANTAGONIST INCLUDE.....

SB-269,970 (GlaxoSmithKline) @TOCRIS
Amisulpride (an anti-depressant/anti-psychotic agent)

Though Turmeric/Curcumin isn't specifically a 5-HT7 Receptor Antagonist - it does PREVENT Stress-Induced Increases in 5-HT(7) Receptor Expression.

**CORE CITATIONS**

The 5-HT7 receptor and disorders of the nervous system: an overview