Protection by an adenosine analogue against kainate-induced extrahippocampal neuropathology.
1. The glutamate analogue kainic acid produces neuronal damage in the central nervous system. We have reported that analogues of adenosine, such as R-N6-phenylisopropyladenosine (R-PIA) can, at doses as low as 10 microg/kg IP, prevent the hippocampal damage that follows the systemic administration of kainate. The present work was designed to examine purine protection against kainate in extrahippocampal regions by using histological methods. 2. The results show that R-PIA, at a dose of 25 microg/kg IP in rats, can protect against the neuronal damage caused by kainate in the basolateral amygdaloid nuclei, the pyriform cortex and around the rhinal fissure. This protection could be prevented by the simultaneous administration of the A1 adenosine receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine, confirming that the protection involved adenosine A1 receptors. No protection was observed in the posterior amygdaloid nuclei or the entorhinal cortex, suggesting the absence of relevant adenosine receptors or a different mechanism of excitotoxicity.
Division of Neuroscience and Biomedical Systems, University of Glasgow, Scotland.
D G
DG
MacGregor
D I
DI
Graham
P A
PA
Jones
T W
TW
Stone
D000241:Adenosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000679:Amygdala / Q000187:drug effects; D000818:Animals; D001921:Brain / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects; D018728:Entorhinal Cortex / Q000187:drug effects; D007608:Kainic Acid / Q000037:antagonists & inhibitors*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013788:Thalamus / Q000187:drug effects
C047235:N-(1-methyl-2-phenylethyl)adenosine; D000241:Adenosine; D007608:Kainic Acid