- Title
- Effect of subchronic administration of tachykinin antagonists on response of guinea-pigs to mild and severe stress
- Creator
- Anderson, Wayne; Newson, Penny; Skeri, Maria; Janssen, Norma; Milne, Stephen; Yip, Jane; Jungnickel, Sebastian; Lynch-Frame, Ann; Chahl, Loris A.
- Relation
- Regulatory Peptides Vol. 168, Issue 1-3, p. 59-68
- Publisher Link
- http://dx.doi.org/10.1016/j.regpep.2011.03.006
- Publisher
- Elsevier
- Resource Type
- journal article
- Date
- 2011
- Description
- The effects of subchronic subcutaneous treatment with tachykinin receptor antagonists over nine days on the repeated mild stress response induced by daily subcutaneous injections and on the severe acute stress induced by morphine withdrawal were investigated in guinea-pigs. The NK₁ receptor antagonist, L733,060, 0.25 mg/kg, significantly increased locomotor activity of guinea-pigs compared with animals subjected to repeated injection of the inactive enantiomer, but inhibited Fos-like immunoreactivity (Fos-LI) in the hypothalamus. In animals subjected to the acute severe stress of naltrexone-induced morphine withdrawal, treatment with the NK₁ antagonist, L733,060, produced reductions in Fos-LI in the spinal dorsal horn, whereas those treated with the NK₃ antagonist, SSR146,977, 0.3 mg/kg, had reduced Fos-LI in the dorsal horn, adrenal medulla, nucleus accumbens, ventral tegmental area and periaqueductal grey. Those animals treated with both NK₁ and NK₃ antagonists also had reduced Fos-LI in the amygdala and paraventricular nucleus of the thalamus. It was concluded that the NK₁ antagonist reduced the hypothalamic response to mild stress but the NK₃ antagonist was more effective in reducing the severe stress response to morphine withdrawal. Furthermore, combination of NK₁ and NK₃ antagonists was more effective than either antagonist in reducing the Fos-LI response to morphine withdrawal.
- Subject
- NK₁ antagonist; NK₃ antagonist; Fos; central nervous system; adrenal gland; morphine withdrawal
- Identifier
- http://hdl.handle.net/1959.13/936563
- Identifier
- uon:12344
- Identifier
- ISSN:0167-0115
- Language
- eng
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