Summary of HTR1A

Summary of Effects of 5HT1A Activation

The following are some effects of 5-HT_1A activation: (R)

The Good:

Stimulates vagus nerve
Reduces fatigue. People with CFS were found to have fewer 5HT1A receptors (R).
Increases sociability – partly from oxytocin and endorphins maybe
Increases sex drive and arousal
Improves some kinds of learning – improves cognitive functions associated with the prefrontal cortex, possibly via inducing prefrontal cortex dopamine and acetylcholine release.
Increases dopamine– in the medial prefrontal cortex, striatum, and hippocampus, which could be beneficial for Schizophrenia and Parkinson’s.
Decreases aggression
Decreases food intake
Decreases blood pressure and heart rate via by stimulating the vagus nerve (rostral ventrolateral medulla).
Decreases impulsivity
Decreases nausea
Decreases body temperature/Cools you…Vasodilation of the blood vessels in the skin increases heat loss…
Decreases pain perception (R) and substance P (cause of pain, inflammatory) – mediated by 5-HT_1A receptors in the dorsal raphe nucleus…..Experiments in rodents suggest that 5-HT1A activation (specifically in the brainstem’s raphe nuclei) causes a perception of relatively less pain with a mild pain stimulus, but relatively more pain when exposed to a more intense pain-stimulus. These animal studies are supported by genetic studies. (R) 5HT1A receptors combine with mu-opioid receptors to cause a numbing of pain, and activating the 5HT1A receptor should cause pain relief (R). There is a substantial connection between depressive disorders and chronic pain and serotonin dysregulation is one such mechanism likely to be shared by both disorders (R). (Think fibromyalgia…)
Decreases drug-seeking
Reverses opioid-induced respiratory depression.

The Bad:

Inhibition of penile erection
Takes longer to get to REM sleep
Impairs certain aspects of memory and learning – due to interference with memory-encoding mechanisms and by inhibiting the release of glutamate and acetylcholine in various areas of the brain.
In the raphe nucleus, 5HT1A autoreceptor activation causes rats to be less active (R).

Neutral:

Causes pupils to get smaller or contract

5HT1A and Hormones

5-HT_1A receptor activation induces the secretion of the following hormones (R):

Cortisol – one reason why people might have low cortisol isn’t because adrenal fatigue , but because the 5HT1A receptors aren’t being activated.
Corticosterone
ACTH
Oxytocin – contributes to the prosocial, anti-aggressive, and anti-anxiety properties
Prolactin
Growth hormone
Endorphins (beta) – contributes to anti-depressant, anti-anxiety, and anti-pain effects

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The Function of HTR1A

G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli.

Protein names

Recommended name:

5-hydroxytryptamine receptor 1A

Short name:

G-21

Alternative name(s):

5-HT-1A
5-HT1A
Serotonin receptor 1A

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RS10042486 (HTR1A) ??
RS1364043 (HTR1A) ??
RS1494630 (HTR1A) ??
RS6295 (HTR1A) ??

Top Gene-Substance Interactions

HTR1A Interacts with These Diseases

Disease	Score

Fixes

How to Naturally Modulate 5HT1A Receptors

Melatonin potentiates the 5-HT1A receptor in the hypothalamus, which results in its cooling effects (R).

T3 is effective in both augmenting and accelerating the therapeutic response to antidepressant drugs. When given to animals, it reduced the sensitivity of 5-HT1A (and 5HT1B) auto-receptors (and postsynaptic) in the hypothalamus (R). I do notice an anti-depressant effect when I up my thyroid hormone production with ICES/LLLT.

Estradiol accelerates the effects of fluoxetine (SSRI) on these receptors, presumably by blunting the increase in 5HT1A autoreceptors from SSRIs in the hypothalamus (PVN) (R).

Exercise (aerobic) increases 5HT1A receptors in the dorsal raphe when they were reduced in an animal stress model (R).

DHA prevented negative effects of a high-fat diet on the 5-HT1A receptor (R).

Omega 3’s/Fish Oil …When animals were fed diets low in Omega-3’s (ALA), 5-HT1A receptors decreased, causing the SSRI not to work properly (R).

Magnesium and Calcium (divalent cations) increase the binding of serotonin to the 5HT1A receptors in the cortex (Purkinje cells) (R). Manganese also helps 5HT1A activators bind better. (R),

Lithium increases 5HT1A postsynaptic sensitivity, while not changing the autoreceptors and it’s thought that this is in part responsible for its anti-depressant activity (R).

Zinc acts as a blocker of the 5HT1A receptor and prevents the binding of this receptor (R). However, it also helps block the combining of the 5HT1A receptor and another receptor (galanin 1), which results in an anti-depressive effect (R).

Butyrate increases 5-HT1A receptors in the hypothalamus, which should result in a similar effect. (R)

St John’s Wort increases the number of postsynaptic 5-HT_1A (and 5-HT_2A) receptors (R).

Rhodiola increases the number of 5HT1A receptors (R).

Ashwagandha decreases 5-HT1A signaling (R).

Fixes Advanced

Other Ways to Modulate 5HT1A Receptors

Curcumin (R),
Ginger is a partial activator of 5HT1A (R),
Bitter orange essential oil (R),
CBD (partial) (R, R2),
Kudzu root/Puerarin (R),
Hesperidin (R)
Yohimbine (R)
Ginkgo (R)

Drugs:

Buspirone (R),
Shrooms/Psilocybin (R),
MDMA or the pure version of ecstasy increases feelings of love, empathy, and connection to others by stimulating oxytocin activity primarily via activation of the 5-HT1A receptors (R).
Quetiapine (R),
Amphetamines (R),
LSD (R).

Chronic intake of SSRIs induces less sensitivity of the auto- and post-synaptic 5-HT1Areceptors in the hypothalamus, so it’s both good and bad, but better than not for some people (R).

Chronic exposure to cortisol desensitizes 5-HT1A autoreceptors receptors (R).

Chronic Transcranial Magnetic Stimulation (rTMS) reduces the sensitivity of post-synaptic 5-HT1A receptors in the hypothalamus, and the study says that “this may be significant in relation to the therapeutic mechanism of rTMS.” (R)

Berberine decreases the serotonergic system by activation of 5-HT1A autoreceptors and inhibition of postsynaptic 5-HT1A and 5-HT2 receptors. Since serotonin is mainly an excitatory neurotransmitter, this effect decreased anxiety in animals (R).

Substances That Increase HTR1A

Category:

Substances	Interaction	Organism	Category

Substances That Decrease HTR1A

Category:

Substances	Interaction	Organism	Category

Conditions with Increased Gene Activity

Experimental Variables:

Condition	Change (log₂fold)	Comparison	Species	Experimental variables	Experiment name

Conditions with Decreased Gene Activity

Experimental Variables:

Condition	Change (log₂fold)	Comparison	Species	Experimental variables	Experiment name

Technical

The following transcription factors affect gene expression:

Tissue specificity:

Detected in lymph nodes, thymus and spleen. Detected in activated T-cells, but not in resting T-cells.

Gene Pathways:

Molecular Function:

Biological Processes:

Drug Bank:

*synonyms

Synonyms/Aliases/Alternative Names of the Gene:

hypothetical protein| 5ht1a| 5-HT1A| 5-HT-1A| 5-HT1A receptor| 5htr1a| 5-hydroxytryptamine receptor 1A-alpha| 5-hydroxytryptamine receptor 1A-beta| 5-hydroxytryptamine (serotonin) receptor 1A| 5-hydroxytryptamine (serotonin) receptor 1A, G protein-coupled| adrb2rl1| adrbrl1| AS27_15492| AS28_11480| CB1_000872011| EGK_16528| EH28_11273| G-21| Gpcr18| G-protein coupled receptor 18| guanine nucleotide-binding regulatory protein-coupled receptor| GW7_05879| H920_10840| htr1a-B| N300_04289| N302_08541| N303_02520| N305_12338| N306_15569| N307_07489| N311_06702| N325_03832| PANDA_015985| PFMCD| RAT5HT1A| serotonin 1A receptor| serotonin 5-HT1A receptor| serotonin receptor 1A| serotonin receptor type 1A| UY3_02797| Y1Q_009548| Y956_04870| htr1a

HTR1A (5-hydroxytryptamine receptor 1A)

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