Decreased brain histamine content in hypocretin/
orexin receptor-2 mutated narcoleptic dogs

Nishino S, Fujiki N, Ripley B, Sakurai E,
Kato M, Watanabe T, Mignot E, Yanai K.
Stanford University Center for Narcolepsy,
701B, First Floor, 94304, Palo Alto, CA, USA.
Neurosci Lett 2001 Nov 9;313(3):125-8


A growing amount of evidence suggests that a deficiency in hypocretin/orexin neurotransmission is critically involved in animal and human forms of narcolepsy. Since hypocretin-containing neurons innervate and excite histaminergic tuberomammillary neurons, altered histaminergic neurotransmission may also be involved in narcolepsy. We found a significant decrease in histamine content in the cortex and thalamus, two structures important for histamine-mediated cortical arousal, in Hcrtr-2 mutated narcoleptic Dobermans. In contrast, dopamine and norepinephrine contents in these structures were elevated in narcoleptic animals, a finding consistent with our hypothesis of altered catecholaminergic transmission in these animals. Considering the fact that histamine promotes wakefulness, decreases in histaminergic neurotransmission may also account for the sleep abnormalities in hypocretin-deficient narcolepsy.

Modafinil: structure
Modafinil and serotonin
Modafinil and the aviator
Orexins to treat narcolepsy
Modafinil and the marmoset
Modafinil: pharmacokinetics
Modafinil as an antidepressant
Modafinil versus amphetamine
Modafinil and histamine release
Modafinil versus methylphenidate
Modafinil v amphetamine v placebo
Narcolepsy and sleep disorders: resources