Histamine

links: reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3389384/ https://raypeatforum.com/community/threads/studies-on-histamines-effects.34971/post-556661 4-18-2021

Histamine #

• Monoamine. Created from Histidine via Histidine Decarboxylase expressed in the Tuberomamillary Nucleus. Deactivated by Histamine Methyltransferase/MAO-B or DAO.

Receptors: H1 (Gq), H2 (Gs), H3 (Gi), and H4 (Gi; peripheral).

• Peaks during the day and gets lower the deeper sleep goes.
• Strongly triggers the release of stomach acid/Bile.
• High histamine can cause hypercalcemia R
• Significantly increases DHT synthesis R
• Estrogen, Corticotrophin-releasing hormone, and Serotonin promote release
• Vitamin D and Vitamin C can lower it Excess histamine can induce acidosis R
• https://men-elite.com/2020/01/03/the-high-dopamine-histamine-personality/
  • Excess histamine can lead to a type A personality. And hyperactivity, OCD, perfectionism, irritation, addiction… This can also lead to a decrease in dopamine.
  • The difference between histamine and dopamine is that dopamine mostly promotes exploration of things outside the comfort-zone, whereas histamine mostly promotes exploration inside the comfort-zone and makes you prone to forming habits.
  • 5-HT2C enhances its release: Brain Histamine Is Crucial for Selective Serotonin Reuptake Inhibitors’ Behavioral and Neurochemical Effects
  • H2 activation can lead to aggression.
• The wake-promoting transmitter histamine preferentially enhances α-4 subunit-containing GABAA receptors GABA-A enhancement? Crazy.
  • GABA-histamine cross-talk may occur preferentially at low GABA concentrations, which could theoretically be inhibitory (via enhancing tonic inhibition), directly excitatory (via enhancing presynaptic GABAergic signaling), or indirectly excitatory (via inhibiting GABAergic interneurons).

Histadelia vs Histapenia #

• Carl C. Pfeiffer piooneered this concept in studying Schizophrenia.
  • He wrote books on orthomolecular medicine.
• Low histamine, due to lower Stomach Acid, can lead to allergies. Possibly more susceptible than high histamine.

Neurotransmission #

Does not cross the BBB.

• Histamine and motivation (2012)
  • Promotes the release of estrogen and oxytocin.
  • Rats entrained dto a specific feeding window wake up in anticipation of the food, and this is related to transient activation of the Tuberomamillary Nucleus (1hr before) and not other areas like orexin neurons, which only activate well after whereupon the TMN activation disappears.
  • In addiction, histamine would amplify the incentive salience of reinforces and associated cues.
  • Mice lacking Histidine Decarboxylase show decreased spatial novelty-induced arousal and reduced exploratory activity in an open field but normal habituation to the same open field
  • Mice lacking H1 show reduced exploratory behavior in (and emotional responses to) novel environments. They do not generate a place preference conditioned by the novel object, but they do explore new objects in a familiar setting.
• The learning of fear extinction
  • Fear extinction depends on NMDA receptor activation. It is positively modulated by D-Serine acting on the glycine site of NMDA receptors
  • Thus, together with D-Serine, the brain histamine system appears as the most generalized, powerful and consistent positive modulator system of the memory consolidation of extinction.
• Acetylcholine, histamine, and cognition: two sides of the same coin (2015)
  • Local administration of histamine failed to affect ACh release from the hippocampus, but:
    • Improvement in fear memory by histamine-elicited ERK2 activation in hippocampal CA3 cells
      • Improved fear memory by H2 or H3 elicited ERK2 activation in hippocampal CA3 cells. Notice how this is H3 enhancing consolidation while it seems to act in opposition to retrieval.
  • The efferent histaminergic fibers of the Tuberomamillary Nucleus are mostly unmyelinated and make relatively few synaptic contacts.
  • Histamine receptors are all characterized by constitutive activity: they are mostly agonist-independent. H3 has the highest.
  • Histidine decarboxylase knockout mice show increased REM (paradoxical sleep)

• The role of histamine on cognition #

Behavior #

Histamine (together with acetylcholine) promotes exploration inside the comfort zone (as opposed to outside, in the case of dopamine); forming habits. It can create a rigid, manic or OCD-like personality; perfectionistic. Can also make you hyper-emotional, as it promotes release of estrogen and Oxytocin. Excess histamine and low dopamine can cause hypervigilance (an intriguing condition) (possibly because histamine promotes release of serotonin?)

• Enhancing dopaminergic signaling and histone acetylation promotes long-term rescue of deficient fear extinction
• Blockade of dopamine activity in the nucleus accumbens impairs learning extinction of conditioned fear
• https://raypeatforum.com/community/threads/the-abundant-energy-legacy.40566/post-677295
  • Low histamine signs:
    • Heavy growth of body hair
    • Grandeur
    • Undue suspicion
    • Racing thoughts
    • Feeling that someone is controlling your mind
    • Ringing in ears
    • Food sensitivities
    • Inability to orgasm; low libido
    • Depressed metabolism