This Article Full Text (PDF) All Versions of this Article: 0269881107076369v1 21/7/757    most recent References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Ishida, T. Articles by Nishikawa, T. Search for Related Content PubMed PubMed Citation Articles by Ishida, T. Articles by Nishikawa, T. Social Bookmarking                         What's this?

Effect of acetaminophen, a cyclooxygenase inhibitor, on Morris water maze task performance in mice

Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan, Department of Oral Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan

Tomoaki Sato

Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan, tomsato{at}dentb.hal.kagoshima-u.ac.jp

Masahiro Irifune

Department of Dental Anesthesiology, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi, Hiroshima, Kagoshima, Japan

Koh-ichi Tanaka

Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan

Norifumi Nakamura

Department of Oral Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan

Takashige Nishikawa

Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan

Although the mechanism of action of acetaminophen (AAP) is not fully understood, some studies suggest that AAP and phenacetin (PHE) are selective cyclooxygenase (COX)-3 inhibitors. To examine the participation of COX-3 in memory formation, water maze performance was studied in mice treated with AAP, PHE or other COX inhibitors. Mice received intraperitoneal injections of drugs immediately after each training session. Administration of high-dose AAP [302.3 mg/kg (IC50 for COX-2)] or PHE [179.2 mg/kg (IC50 for COX-2)] and of non-specific (indomethacin: 20 mg/kg) or specific COX-2 (NS-398: 10 mg/kg) inhibitor impaired the performance in hidden platform (HP) not visible platform (VP) tasks, whereas low-dose (15.1 mg/kg) AAP facilitated performance in HP and VP tasks. The facilitation of performance by low-dose AAP was reversed by co-administration with a 5-HT1/2 receptor antagonist (methysergide: 0.47 mg/kg). The middle-dose [69.5 mg/kg (IC50 for COX-3)] of AAP, the PHE [17.9 mg/kg (IC50 for COX-3)] and a specific COX-1 inhibitor (piroxicam: 10—20 mg/kg) did not influence performance in either task. These results suggest that the memory impairment by high-dose AAP and PHE and facilitation of performance by low-dose AAP could involve endogenous COX-2 and serotonergic neuronal activity, but not COX-3, respectively.

Key Words: mice • acetaminophen • water maze • memory • learning • COX-3 inhibitor

This version was published on September 1, 2007

Journal of Psychopharmacology, Vol. 21, No. 7, 757-767 (2007)
DOI: 10.1177/0269881107076369


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?