Senktide-induced gerbil foot tapping behaviour is blocked by selective tachykinin NK₁ and NK₃ receptor antagonists

详细信息    查看全文

• 作者：Monika Sundqvist ; Elin Kristensson ; Rebecka Adolfsson ; Agnes Leffler ; Ingela Ahlstedt ; Susanna Engberg ; Tomas Drmota ; Kalle Sigfridsson ; Rainer Jussila ; Jennie de Verdier ; Anna Nové ; n ; Anders Joha
• 关键词：Gerbil foot tap ; Neurokinin ; Senktide ; Tachykinin receptor ; Tachykinin receptor antagonist
• 刊名：European Journal of Pharmacology
• 出版年：2007
• 出版时间：22 December 2007
• 年：2007
• 卷：577
• 期：1-3
• 页码：78-86
• 全文大小：335 K

文摘

Intracerebroventricular (i.c.v.) administration of tachykinin NK₁ receptor agonists induces tapping of the hind legs in gerbils, so-called gerbil foot tapping, which is thought to reflect a fear-related response. The aim of the present study was to examine how ligands selective for NK₁, NK₂ and NK₃ receptors affect the gerbil foot tap response. Agonists selective for NK receptor subtypes were administered i.c.v. and the gerbil foot tap response was monitored. The effect of systemically administered antagonists was also studied. The interaction of ligands with gerbil NK₁ receptors was evaluated using autoradiography on gerbil brain slices with [³H]-Sar,Met(O₂)-substance P or [³H]GR205171 as radioligand. The effects of ligands on NK₁ and NK₃ receptor-mediated increases in intracellular calcium in vitro were studied in Chinese hamster ovary cells expressing the cloned gerbil receptors. The selective NK₁ receptor agonist ASMSP and the selective NK₃ receptor agonist senktide induced dose-dependent increases in gerbil foot tapping with similar potency. The maximal effect of senktide was approximately 40 % of the maximal response evoked by ASMSP. The effects of ASMSP and senktide were blocked by administration of the selective NK₁ receptor antagonist CP99,994 (10 μmol/kg s.c.). The effects of senktide, but not ASMSP, were blocked by administration of the selective NK₃ receptor antagonist SB223412 (50 μmol/kg i.p.). Senktide did not displace NK₁ receptor radioligand binding and was > 1000-fold less potent than ASMSP at activating gerbil NK₁ receptors. The selective NK₃ receptor agonist senktide evokes fear-related gerbil foot tapping, an effect which probably involves indirect enhancement of NK₁ receptor signalling.