WAY 100635, a 5-HT1A receptor antagonist, prevents the impairment of spatial learning caused by blockade of hippocampal NMDA receptors

We studied the effect of WAY 100635, a 5-HT1A receptor antagonist, on the i mpairment of spatial learning caused by intrahippocampal injection of 3-((R )-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), a competitive NMD A receptor antagonist, in a two-platform spatial discrimination task. CPP, 3 and 10 ng/mu l, administered bilaterally into the CA1 region of the dorsa l hippocampus 10 min before each training session, dose-dependently reduced choice accuracy in the two-platform spatial discrimination task with littl e or no effect on choice latency and errors of omission. A volume of 10 ng/ mu l intrahippocampal CPP did not affect choice accuracy or latency of a no n-spatial visual discrimination task. Subcutaneous doses of 0.3 and 1 mg/kg WAY 100635 did not modify the choice accuracy, but prevented the impairmen t caused by 10 ng/mu l intrahippocampal CPP. A dose of 20 ng/mu l WAY 10063 5 into the dorsal hippocampus prevented the deficit caused by 10 ng/yl CPP administered in the same region. The results suggest that blockade of 5-HT1 A receptors can compensate the loss of NMDA-mediated excitatory input to py ramidal cells in the hippocampus. These findings may have clinical relevanc e for the symptomatic treatment of memory disorders associated with reduced glutamate transmission mediated by NMDA receptors. (C) 1999 Published by E lsevier Science Ltd. All rights reserved.