1. ¹Department of Biomedical Sciences, AVC, University of Prince Edward Island, Charlottetown, PE, Canada
2. ²Canada National Institute for Nutrisciences and Health, Charlottetown, PE, Canada
3. ³Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada

Correspondence: Dr C Song, Department of Biomedical Sciences, AVC, University of Prince Edward Island and NRC Institute for Nutrisciences and Health, 93 Mount Edward Road, Charlottetown, PE, Canada C1A 5T1, Tel: +1 902 566 7977, Fax: +1 902 569 4289, E-mail: cai.song@nrc.gc.ca

Received 18 October 2005; Revised 26 April 2006; Accepted 1 May 2006; Published online 14 June 2006.

Abstract

Previously, we have reported that interleukin-1 (IL-1) induces changes in dopaminergic (DA) and serotonergic systems in the core of nucleus accumbens (NAc). We have also demonstrated that n-3 fatty acid ethyl-eicosapentaenoate (EPA) can significantly reduce stress and anxiety-like behaviors, corticosterone concentration and peripheral inflammatory response induced by IL-1 administration. Compared to the core, the shell is involved more in emotion, stress and psychiatric diseases. However, the relationship between inflammation and the functions of DA system in the shell has not been studied. Since phospholipase (PL) A2 is a key enzyme in arachidonic acid (AA)- eicosanoids-prostaglandin (PG)E2 pathway, and the change in NAc dopaminergic system has been associated with glucocorticoid stimulation, therefore, the hypotheses of this study are (1) that IL-1 induced changes in DA neurotransmission in the shell may be through PLA2-PGE2-corticosterone pathway; (2) EPA may attenuate IL-1 effects via inhibiting PLA2 activities, which blocks PGE2 stimulation of corticosterone. Using an in vivo microdialysis method, the present study showed that IL-1 administration significantly increased extracellular levels of DA, and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the shell of the NAc. IL-1 also increased blood concentration of corticosterone and PGE2, and increased the activities of cytosolic and sectory of PLA2. IL-1-induced changes were significantly attenuated by EPA treatment. Furthermore, glucorcoticoid receptor antagonist mifepristone (RU486) pretreatment significantly blocked IL-1-induced changes in DA and metabolites. Qquinacrine, a PLA2 antagonist significantly blocked IL-1 induced increase in PGE2 and corticosterone concentrations. These results demonstrated the hypotheses that IL-1 effects may be via PLA2-PGE2-corticosterone pathway and EPA attenuated IL-1 effects may be through the suppression of PLA2 expression, which then reduced PGE2 synthesis and corticosterone secretion.