PT  - JOURNAL ARTICLE
AU  - Pierre Blier
AU  - Gabriella Gobbi
AU  - Nasser Haddjeri
AU  - Luca Santarelli
AU  - Gina Mathew
AU  - René Hen
TI  - Impact of substance P receptor antagonism on the serotonin and norepinephrine systems: relevance to the antidepressant/anxiolytic response
DP  - 2004 May 01
TA  - Journal of Psychiatry and Neuroscience
PG  - 208--218
VI  - 29
IP  - 3
4099  - http://jpn.ca/content/29/3/208.short
4100  - http://jpn.ca/content/29/3/208.full
SO  - JPN2004 May 01; 29
AB  - Substance P (neurokinin-1 [NK1]) receptor antagonists appear to be effective antidepressant and anxiolytic agents, as indicated in 3 double-blind clinical trials. In laboratory animals, they promptly attenuate the responsiveness of serotonin (5-hydroxytryptamine [5-HT]) and norepinephrine (NE) neurons to agonists of their cell-body autoreceptors, as is the case for some antidepressant drugs that are currently in clinical use. Long-term, but not subacute, antagonism of NK1 receptors in rats increases 5-HT transmission in the hippocampus, a property common to all antidepressant treatments tested thus far. This enhancement seems to be mediated by a time-dependent increase in the firing rate of 5-HT neurons. Mice with the NK1 receptor deleted from their genetic code also have an increased firing rate of 5-HT neurons. Taken together, these observations strongly suggest that NK1 antagonists could become a new class of antidepressant and anxiolytic agents.