S-(+)-fenfluramine-induced nociceptive behavior in mice: Involvement of interactions between spinal serotonin and substance P systems

Tan-No, Koichi; Takahashi, Katsuaki; Shimoda, Masakazu; Sugawara, Mai; Nakagawasai, Osamu; Niijima, Fukie; Sato, Takumi; Satoh, Susumu; Tadano, Takeshi

doi:10.1016/j.npep.2006.10.003

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Volume 41, Issue 1 , Pages 33-38, February 2007

S-(+)-fenfluramine-induced nociceptive behavior in mice: Involvement of interactions between spinal serotonin and substance P systems

Koichi Tan-No
- Department of Pharmacology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
- Corresponding author. Tel.: +81 22 727 0123; fax: +81 22 275 2013.
Katsuaki Takahashi
- Department of Pharmacology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Masakazu Shimoda
- Department of Pharmacology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Mai Sugawara
- Department of Pharmacology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Osamu Nakagawasai
- Department of Pharmacology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Fukie Niijima
- Department of Pharmacology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Takumi Sato
- Department of Pharmacology and Pharmacotherapy, Nihon Pharmaceutical University, Kitaadachi-gun, Saitama 362-0806, Japan
Susumu Satoh
- Department of Pharmacology and Pharmacotherapy, Nihon Pharmaceutical University, Kitaadachi-gun, Saitama 362-0806, Japan
Takeshi Tadano
- Department of Pharmacology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan

Received 12 August 2006; accepted 11 October 2006. published online 01 December 2006.

Abstract

Intrathecal (i.t.) administration into mice of S-(+)-fenfluramine (0.01–0.1nmol), a serotonin (5-hydroxytryptamine, 5-HT) releaser, produced a behavioral response consisting of scratching, biting and licking. Here, we report the behavioral characteristics and the involvement of interactions between 5-HT and substance P (SP) systems in the S-(+)-fenfluramine-induced behavioral response. The S-(+)-fenfluramine-induced behavioral response peaked at 5–15min and almost disappeared at 20min after injection. The behavior induced by S-(+)-fenfluramine (0.1nmol) was dose-dependently inhibited by an intraperitoneal injection of morphine (0.02–0.5mg/kg), suggesting that the behavioral response is related to nociception. The S-(+)-fenfluramine-induced nociceptive behavior was significantly inhibited by pretreatment with 5-HT antiserum and co-administration of ketanserin, a selective 5-HT2 receptor antagonist. However, WAY-100635, a selective 5-HT1A receptor antagonist, and ramosetron, a selective 5-HT3 receptor antagonist, were not active. On the other hand, SP antiserum and RP67580, a selective neurokinin-1 (NK1) receptor antagonist, significantly inhibited S-(+)-fenfluramine-induced nociceptive behavior. These results suggest that i.t.-administered S-(+)-fenfluramine releases SP through the activation of 5-HT2 receptors subsequent to 5-HT release, and, as a result, produces nociceptive behavior.