Working memory failure by stimulation of hippocampal adenosine A1 receptors in rats.

THE highly selective adenosine A1 receptor agonist N6-cyclohexyladenosine (CHA) significantly increased the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) in the working memory task with a three-panel runway setup, when injected bilaterally at 0.3 and 1.0 microgram per side into the dorsal hippocampus. Pretreatment with the selective adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 1 mg kg-1, i.p.) prevented the increase in working memory errors induced by intrahippocampal administration of CHA (1.0 microgram per side). CGS-21680, a highly selective agonist for adenosine A2 receptors, had no effect on the number of working memory errors, when administered intrahippocampally at a dose of 1.0 microgram per side. These results suggest that activation of hippocampal adenosine A1 receptors interferes with neural processes involved in working memory function.