Stress-induced C-fos expression in the rat locus coeruleus is dependent on neurokinin 1 receptor activation.
These experiments examined the role of substance P-selective neurokinin 1 receptors in the restraint-induced activation of the rat locus coeruleus. Immunohistochemistry revealed high levels of neurokinin 1 receptor expression in the plasma membrane of tyrosine hydroxylase-positive locus coeruleus neurons. The selective neurokinin 1 receptor antagonists, RP 67580 (5 nmol) and L-760,735 (3.4 nmol), were administered intracerebroventricularly prior to restraint stress, and c-fos protein was measured as an index of locus coeruleus activation. Both antagonists attenuated the restraint-induced increase in locus coeruleus c-fos expression, whereas their inactive enantiomers were ineffective. These results suggest that neurokinin 1 receptors may mediate activation of locus coeruleus neurons during stress. Neurokinin 1 receptor antagonists may prove to be novel therapeutic compounds in the treatment of anxiety and depression.
Hahn
M K
MK
Department of Psychiatry, Wayne State University of Medicine School, Detroit, MI 48201, USA.
Bannon
M J
MJ
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology; D007276:Injections, Intraventricular; D054833:Isoindoles; D008125:Locus Coeruleus / Q000378:metabolism*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D007211:Indoles; D054833:Isoindoles; C114226:L 760735; D009025:Morpholines; D064729:Neurokinin-1 Receptor Antagonists; D016760:Proto-Oncogene Proteins c-fos; D018040:Receptors, Neurokinin-1; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D014446:Tyrosine 3-Monooxygenase