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Re: modafinil » SLS

Posted by zeugma on September 21, 2005, at 19:51:48

In reply to Re: modafinil » zeugma, posted by SLS on September 21, 2005, at 17:54:24

> Modafinil's activation of orexin receptors appears to be secondary to its ability to release histamine (the orexinergic system is activated by histamine).>>

I thought it was the other way around. Oh well.>

It seems that we're both right, and interactions are reciprocal between the two systems:

Orexin/hypocretin excites the histaminergic
neurons of the tuberomammillary nucleus
by
Eriksson KS, Sergeeva O, Brown RE, Haas HL.
Institute for Neurophysiology,
Heinrich-Heine-Universitat,
D-40225 Dusseldorf, Germany.
J Neurosci 2001 Dec 1;21(23):9273-9

ABSTRACT
The hypothalamic orexin (hypocretin) neuropeptides are associated with the regulation of sleep and feeding, and disturbances in orexinergic neurotransmission lead to a narcoleptic phenotype. Histamine has also been shown to play a role in the regulation of sleep and feeding. Therefore, we studied the relationship between the orexin and histamine systems of the CNS using electrophysiology, immunocytochemistry, and the reverse transcriptase (RT)-PCR method. Both orexin-A and orexin-B depolarized the histaminergic tuberomammillary neurons and increased their firing rate via an action on postsynaptic receptors. The depolarization was associated with a small decrease in input resistance and was likely caused by activation of both the electrogenic Na(+)/Ca(2+) exchanger and a Ca(2+) current. In a single-cell RT-PCR study using primers for the two orexin receptors, we found that most tuberomammillary neurons express both receptors and that the expression of the orexin-2 receptor is stronger than that of the orexin-1 receptor. Immunocytochemical studies show that the histamine and orexin neurons are often located very close to each other. The contacts between these two types of neurons seem to be reciprocal, because the orexin neurons are heavily innervated by histaminergic axons. These results suggest a functional connection between the two populations of hypothalamic neurons and that they may cooperate in the regulation of rapid-eye-movement sleep and feeding.

-z


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poster:zeugma thread:557238
URL: http://www.dr-bob.org/babble/20050921/msgs/557843.html