Prostaglandins are necessary and sufficient to induce contextual fear learning impairments after interleukin-1 beta injections into the dorsal hippocampus.
The intra-hippocampal administration of interleukin-1beta (IL-1beta) as well as the induction of elevated but physiological levels of IL-1beta within the hippocampus interferes with the formation of long-term memory. There is evidence suggesting that the induction of prostaglandin (PG) formation by IL-1beta is involved in impairments in working and spatial memory following IL-1beta. The present experiments extend these findings by showing that PGs are responsible for memory deficits in contextual fear conditioning that occur following IL-1beta injection into the dorsal hippocampus of Sprague-Dawley rats. Cyclooxygenase (COX) inhibition blocked the disruption in contextual fear conditioning produced by IL-1beta and COX inhibition alone also disrupted contextual memory, suggesting an inverted U-shaped relationship between PG levels and memory. In addition to demonstrating the necessity of PGs in IL-1beta-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.
Department of Psychology and The Center for Neuroscience, University of Colorado at Boulder, Campus Box 345, Boulder, CO 80309, USA. amy.hein@colorado.edu
A M
AM
Hein
D L
DL
Stutzman
S T
ST
Bland
R M
RM
Barrientos
L R
LR
Watkins
J W
JW
Rudy
S F
SF
Maier
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects*; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005239:Fear; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D053583:Interleukin-1beta / Q000009:adverse effects*; D007859:Learning Disabilities / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D009288:Naproxen / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D053583:Interleukin-1beta; D011453:Prostaglandins; D009288:Naproxen; D015232:Dinoprostone