RT Journal Article
SR Electronic
T1 Impact of substance P receptor antagonism on the serotonin and norepinephrine systems: relevance to the antidepressant/anxiolytic response
JF Journal of Psychiatry and Neuroscience
JO JPN
FD Canadian Medical Association
SP 208
OP 218
VO 29
IS 3
A1 Pierre Blier
A1 Gabriella Gobbi
A1 Nasser Haddjeri
A1 Luca Santarelli
A1 Gina Mathew
A1 René Hen
YR 2004
UL http://jpn.ca/content/29/3/208.abstract
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.