Tachykinin NK1 receptor antagonists enhance stress-induced c-fos in rat locus coeruleus.
These experiments tested the hypothesis that substance P neurotransmission at tachykinin NK1 receptors in the locus coeruleus is involved in stress-induced activation of the locus coeruleus, using c-fos as an index of activation. Selective tachykinin NK1 receptor antagonists administered systemically did not result in substantial locus coeruleus c-fos expression. Restraint stress resulted in a large number of locus coeruleus c-fos expressing cells. Administration of two selective tachykinin NK1 receptor antagonists prior to restraint resulted in an increase in the number of locus coeruleus c-fos expressing cells, compared to restraint alone. These results suggest that the enhanced c-fos expression observed in response to tachykinin NK1 receptor antagonists combined with stress, could be due to the blockade of tachykinin NK1 receptor-mediated activity at sites other than the locus coeruleus, resulting in an overall activation of the locus coeruleus.
Hahn
M K
MK
Department of Psychiatry and Behavioral Neurosciences, Wayne State University Medical School, Detroit, MI 48201, USA.
Bannon
M J
MJ
D000081:Acetamides / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D012149:Restraint, Physical; D013237:Stereoisomerism; D013312:Stress, Physiological / Q000209:etiology / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics
D000081:Acetamides; D000700:Analgesics; D007211:Indoles; D054833:Isoindoles; C102280:LY 306740; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011812:Quinuclidines; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; C085215:SR 140333; D013373:Substance P