The substance P antagonist L-760,735 inhibits stress-induced NK(1) receptor internalisation in the basolateral amygdala.
The distribution of NK(1) receptor immunoreactivity in the amygdaloid complex, induction of NK(1) receptor endocytosis in the amygdala following immobilisation stress, and the ability of pretreatment with the substance P antagonist L-760,735 or imipramine to block this response were examined in gerbils, a species with human-like NK(1) receptor pharmacology. Highest levels of immunolabelling were observed in the anterior, amygdalo-hippocampal and medial nuclei. Less dense labelling was observed in the basolateral nucleus, where it was possible to clearly visualise the distal dendrites of NK(1) immunoreactive neurones and quantify the effect of immobilisation stress on NK(1) receptor endocytosis morphology, a marker of local substance P release. Immobilisation for 1 h caused an approximately 60% increase in the number of dendritic processes undergoing NK(1) receptor endocytosis in the basolateral amygdala that was inhibited by acute pretreatment of animals with L-760,735 (3 mg/kg), but not by imipramine (10 mg/kg). These findings are consistent with other evidence that the amygdala represents a possible site of action for the antidepressant and anxiolytic efficacy of substance P antagonists.
Smith
D W
DW
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, UK.
Hewson
L
L
Fuller
P
P
Williams
A R
AR
Wheeldon
A
A
Rupniak
N M
NM
D000679:Amygdala / Q000166:cytology / Q000187:drug effects*; D000818:Animals; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005849:Gerbillinae; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D018040:Receptors, Neurokinin-1 / Q000032:analysis* / Q000187:drug effects*; D013312:Stress, Physiological / Q000378:metabolism*; D013373:Substance P / Q000037:antagonists & inhibitors*
C114226:L 760735; D009025:Morpholines; D018040:Receptors, Neurokinin-1; D013373:Substance P; D007099:Imipramine