WAY-100635, A 5-HT1A RECEPTOR ANTAGONIST, PREVENTS THE IMPAIRMENT OF SPATIAL-LEARNING CAUSED BY INTRAHIPPOCAMPAL ADMINISTRATION OF SCOPOLAMINE OR 7-CHLORO-KYNURENIC ACID

The effect of WAY 100635, a 5-HT1A receptor antagonist, on the impairm ent of spatial learning caused by intrahippocampal administration of s copolamine, a cholinergic muscarinic receptor antagonist, or 7-chloro- kynurenic acid, an antagonist at the glycine site associated with the NMDA receptor complex, was studied in a two-platform spatial discrimin ation task. Scopolamine (4 mu g/mu l) or 7-chloro-kynurenic acid (3 mu g/mu l), administered bilaterally into the CA1 region of the dorsal h ippocampus 10 min before each training session, impaired choice accura cy with no effect on choice latency and errors of omission. Administer ed subcutaneously at 1 (but not at 0.3) mg/kg 30 min before each train ing session, WAY 100635 did not modify the acquisition of spatial lear ning, but prevented the impairment of choice accuracy caused by intrah ippocampal scopolamine or 7-chloro-kynurenic acid. These findings sugg est that blockade of 5-HT1A receptors can compensate the loss of choli nergic or NMDA-mediated excitatory input to pyramidal cells in the hip pocampus. The mechanisms involved and the importance of these findings for the symptomatic treatment of memory disorders in man are discusse d. (C) 1997 Elsevier Science B.V.