Selective blockade of N-methyl-D-aspartate channels in combination with dopamine receptor antagonism induces loss of the righting reflex in mice, but not immobility

Nobuhito Kikuchi, Masahiro Irifune, Yoshitaka Shimizu, Keita Yoshida, Katsuya Morita, Takashi Kanematsu, Norimitsu Morioka, Yoshihiro Nakata, Norio Sakai

研究成果: ジャーナルへの寄稿学術誌査読

1 被引用数 (Scopus)

抄録

Rationale: The selective N-methyl-D-aspartate (NMDA) channel blocker MK-801 is known to induce no loss of the righting reflex (LORR) and to stimulate catecholaminergic (CAergic) neurons in rodents, playing a crucial role in arousal. Objectives: We examined whether MK-801 in combination with CA receptor ligands, which inhibit CAergic neuronal activities, could induce anesthesia including LORR. Methods: All drugs were administered systemically to mice. To assess anesthesia, three different behaviors were used: loss of nociceptive response (analgesia in the free-moving state without LORR), LORR, and loss of movement in response to noxious stimulation (immobility under LORR). Results: A very large dose of MK-801 (50 mg/kg) induced neither analgesia nor LORR. In contrast, MK-801 in combination with a small dose of the dopamine (DA) receptor antagonist haloperidol (0.2 mg/kg) dose-dependently produced LORR with a 50 % effective dose (ED50) of 1.6 (0.9-3.0; 95 % confidence limit) mg/kg, but not immobility. The α2-adrenoceptor agonist dexmedetomidine induced not only analgesia, but also immobility in animals treated with MK-801 (5 mg/kg) plus haloperidol (0.2 mg/kg), which then lost their righting reflex. The ED50 value of 0.26 (0.10-0.66) mg/kg (various doses of dexmedetomidine plus a fixed dose of MK-801 and haloperidol) for immobility was approximately three-fold larger than that of 0.09 (0.03-0.23) mg/kg (dexmedetomidine plus vehicle saline) for analgesia. This may occur, as LORR induced by MK-801 plus haloperidol inhibits the pain suppression system. The other ligands had little or no effect. Conclusions: The DAergic stimulant actions of MK-801 may mask its LORR effects by NMDA channel blockade.

本文言語英語
ページ(範囲)39-46
ページ数8
ジャーナルPsychopharmacology
232
1
DOI
出版ステータス出版済み - 1月 2015
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 薬理学

フィンガープリント

「Selective blockade of N-methyl-D-aspartate channels in combination with dopamine receptor antagonism induces loss of the righting reflex in mice, but not immobility」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル