The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Sustained blockade of neurokinin-1 receptors enhances serotonin neurotransmission.

BACKGROUND: Antagonists of neurokinin-1 (NK(1)) receptors, through which substance P acts, have been proposed to belong to a new class of antidepressants with a unique mode of action. It was postulated that they exert this putative therapeutic effect independently of the serotonin (5-HT) neurons. METHODS: The aim of the present study was to assess, using in vivo electrophysiological paradigms, the effects of sustained administration of the nonpeptidic NK(1) antagonist CP-96,345 on the firing activity of rat dorsal raphe 5-HT neurons, the responsiveness of pre- and postsynaptic 5-HT(1A) receptors, and overall 5-HT neurotransmission in the hippocampus. RESULTS: Both short- and long-term treatments with CP-96,345 significantly increased the spontaneous firing activity of dorsal raphe 5-HT neurons, and this increase was associated with an attenuation of somatodendritic 5-HT(1A) autoreceptor responsiveness. In contrast, the inactive enantiomer of CP-96,345 at NK(1) receptors, CP-96,344, did not alter these parameters after short-term administration. Because 5-HT(1A) receptor activation inhibits the firing activity of dorsal hippocampus CA(3) pyramidal neurons, the degree of disinhibition produced by the selective 5-HT(1A) receptor antagonist WAY 100635 was determined to assess the net change in 5-HT neurotransmission. Intravenous injection of WAY 100635 did not disinhibit CA(3) pyramidal neuron firing in rats given saline, CP-96,345 for 2 days, or CP-96,344 for 14 days, but produced a significant enhancement of firing in rats treated with CP-96,345 for 2 weeks. Therefore, only long-term treatment with CP-96,345 enhanced the tonic activation of postsynaptic 5-HT(1A) receptors. CONCLUSIONS: Similar to all other major types of antidepressant treatments, these data indicate that substance P antagonists might alleviate anxiety and major depression, at least in part, by enhancing the degree of activation of some 5-HT receptors in the forebrain.[1]

References

 
WikiGenes - Universities