The intra-hippocampal administration of interleukin-1β (IL-1β) as well as the induction of elevated but physiological levels of IL-1β within the hippocampus interferes with the formation of long-term memory. There is evidence suggesting that the induction of prostaglandin (PG) formation by IL-1β is involved in impairments in working and spatial memory following IL-1β. The present experiments extend these findings by showing that PGs are responsible for memory deficits in contextual fear conditioning that occur following IL-1β injection into the dorsal hippocampus. Cyclooxygenase (COX) inhibition blocked the disruption in contextual fear conditioning produced by IL-1β and COX inhibition alone also disrupted contextual memory, suggesting an inverted Ushaped relationship between PG levels and memory. In addition to demonstrating the necessity of PGs in IL-1β mediated memory deficits, we also show that PGs injected directly into the dorsal hippocampus are sufficient to impair context memory and significantly reduce post-conditioning levels of BDNF within the hippocampus, suggesting a possible mechanism for the memory-impairing effects of PGs. Keywords memory; brain derived neurotrophic factor; cyclooxygenase; EP receptorThe pro-inflammatory cytokine interleukin-1β (IL-1β) exerts powerful central and peripheral actions. Recently, there has been considerable interest in its influence within the brain on learning and memory. This interest initially derived in part from findings that Alzheimer's disease and AIDS-related dementia are associated with elevated brain levels of IL-1β (Griffen et al., 1989;Lombardi et al., 1999). More direct evidence implicating IL-1β in learning and memory has come from animal studies. Manipulations that increase levels of IL-1β within the hippocampus have been shown to impair memory formation. These manipulations include the injection of the gram-negative bacterial component lipopolysaccharide (LPS;Pugh et al. 1998), social isolation stress (Pugh et al., 1999), and aging (Gemma et al., 2005). The blockade of IL-1 receptors and/or the inhibition of IL-1 synthesis prevents these memory impairments, supporting the conclusion that they are mediated by IL-1β (Pugh et al. 1998;Pugh et al., 1999;Gemma et al., 2005). Moreover, direct injection of IL-1β into the dorsal hippocampus Tel.: +1 303 492 9616; fax: +1 303 492 2967., E-mail address: amy.hein@colorado.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (Barrientos et al., 2002). Consistent with these data, IL-1β potently inhibits long-term potentiation (LTP), a form of synaptic strengthenin...