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-HT_1A receptor antagonist, on the impairment of spatial learning caused by intrahippocampal administration of scopolamine, 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 discrimination task. Scopolamine (4 μg/μl) or 7-chloro-kynurenic acid (3 μg/μl), administered bilaterally into the CA1 region of the dorsal hippocampus 10 min before each training session, impaired choice accuracy with no effect on choice latency and errors of omission. Administered subcutaneously at 1 (but not at 0.3) mg/kg 30 min before each training session, WAY 100635 did not modify the acquisition of spatial learning, but prevented the impairment of choice accuracy caused by intrahippocampal scopolamine or 7-chloro-kynurenic acid. These findings suggest that blockade of 5-HT_1A receptors can compensate the loss of cholinergic or NMDA-mediated excitatory input to pyramidal cells in the hippocampus. The mechanisms involved and the importance of these findings for the symptomatic treatment of memory disorders in man are discussed.