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 (15)
• Increasing Behavioral / Cognitive Flexibility (16)
• Reducing Stress-Induced Anhedonia (17)
• Increasing Resilience / Stress Adaptation (18)
• Increasing Sensitivity to Amphetamine and Blocking the Reduction in Dopamine Induced by Amphetamine (19)

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

• {The medical benefit of 5-HT research}

5-HT7 receptors as modulators of neuronal excitability, synaptic transmission and plasticity: physiological role and possible implications in autism spectrum disorders

Targeting the Serotonin 5-HT7 Receptor in the Search for Treatments for CNS Disorders: Rationale and Progress to Date

Functional, molecular andpharmacological advances in 5-HT7receptor research

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Serotonin, stress and corticoids

1. Stress- and antidepressant treatment-induced modifications of 5-HT₇ receptor functions in the rat brain.
2. Cellular mechanisms of the 5-HT7 receptor-mediated signaling
3. The serotonin-7 receptor as a novel therapeutic target.

 Epigenetics of stress adaptations in the brain

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