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> Histaminergic Potentiation
post Feb 19, 2007, 03:15 PM
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does anyone know anything about this? Apparently, histaminergic fibers from the tuberomammillary nucleus in the posterior hypothalamus innervate the entire cortex and thalamus in a manner similar to other neuromodulators, like serotonin and norepinephrine. I know from experience that anti-histamines put me to sleep, so the opposite, potentiating histaminergic function, may lead to increased arousal and vigilance. It would be good to find studies on this.

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post Feb 23, 2007, 02:52 AM
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I found this, maybe of some use. There are some names that may yield a favourable google. I've been following up this topic too, quite interesting me thinks.

From the New York Times, 7-20-04
Scientists Unlock One More of Sleep's Secrets

Human behavior can be reduced to a series of chemical reactions. Sleep, that puzzling but most routine of activities, is no exception.

Scientists have long known that three brain chemicals - serotonin, norepinephrine and histamine - are involved in sleep and waking. They dwindle when people nod off and spike as people wake up. But for the first time, a recent study has found that each of the three neurotransmitters plays a distinct role. The ebb and flow of serotonin and norepinephrine affect muscle tone, keeping the body still at night, the study found, while histamine controls arousal.

The findings could lead to new treatments for sleep disorders and drugs that enhance wakefulness. They might also shed light on the familiar sleep-inducing effects of cold and allergy medications that contain antihistamines, the researchers said.

"This is really the first time we've been able to separate two phenomena that normally go on together," said Dr. Jerome M. Siegel, senior author of the study and chief of neurobiology research at the Veterans Affairs Greater Los Angeles Healthcare System.

The study, based on five years' research and published recently in the journal Neuron, measured brain activity in dogs with narcolepsy, a severe sleep disorder that affects up to 200,000 Americans.

The animals showed patterns of brain signaling similar to those normally found in humans. During wakefulness, levels of histamine, norepinephrine and serotonin were high. In deep sleep, when dreams are most vivid, they dwindled. Sleep experts have traditionally lumped the transmitters together, assuming that they worked together to regulate arousal, and fell silent during rapid eye movement or REM sleep, to keep the body from acting out dreams.

A bizarre symptom of narcolepsy, called cataplexy, that causes patients with the condition to collapse suddenly from loss of muscle tone while fully conscious, showed that this was not the case. A recording device using wires thinner than a human hair detected histamine cells firing as the narcoleptic dogs lay paralyzed but wide awake. Drugs that worsened the condition had no effect on histamine.

Cataplexy, Dr. Siegel said, appears to be the mirror image of REM behavior disorder, a condition that causes people to act out their dreams physically. People with the disorder tend to have vivid dreams, often of being attacked or engaging in active sports. They sometimes end up harming themselves or they open their eyes to find that they are pummeling their bed partners.

"It's likely that they have the reverse pattern - that they're losing consciousness without the loss of muscle tone," said Dr. Siegel, also a professor of psychiatry and biobehavioral sciences at the University of California, Los Angeles. "Now we can actually dissect what's going on."

Sleep is regulated by the activity of histamine cells concentrated in the posterior hypothalamus, just above the pituitary.

Narcolepsy, Dr. Siegel said, appears to be caused by damage to structures that process another neurotransmitter, hypocretin, that in turn leads to lower levels of histamine. Insomniacs, chronically prone to sleepless nights, are probably suffering from the reverse, an excess of histamine. A treatment, he said, could be as simple as finding a drug that suppresses the chemical.

"It seems that consciousness itself must be dependent on histamine neurons being active," said Dr. Peter Shiromani, an associate professor of neurology at Harvard who was not involved with the study.

For researchers looking at drugs to keep people awake, Dr. Shiromani said, "histamine is the way to go."

Stimulants like amphetamines that release norepinephrine and dopamine are often addictive and can lead to psychosis and other dangerous side effects. Caffeine wears off more quickly and causes irritability. But drugs that increase histamine, Dr. Shiromani said, could have powerful effects on arousal with less severe side effects. The problem is that they would have to focus on the central nervous system, crossing the blood-brain barrier without flooding histamine receptors in other parts of the body.

Histamine in the nasal cavity and elsewhere would set off an inflammatory response, along with the watering eyes, sneezing and scratch throat that allergy sufferers know all too well, and that cold and allergy medications are intended to blunt.
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