(S)-WAY 100135, a 5-HT1A receptor antagonist, prevents the impairment of spatial learning caused by intrahippocampal scopolamine.

Scopolamine, 3.75 micrograms/microliters infused bilaterally into the CA1 region of the dorsal hippocampus 10 min before each training session, impaired choice accuracy but had no effect on choice latency or errors of omission in rats trained in a two-platform spatial discrimination task. Administered subcutaneously at 3 and 10 mg/kg 30 min before each training session, N-tert-butyl-3-4-(2-methoxyphenyl)piperazin-1-yl-2-phenylpropanami de dihydrochloride ((S)-WAY 100135), a 5-HT1A receptor antagonist, prevented the impairment of choice accuracy induced by intrahippocampal scopolamine. No subcutaneous dose of (S)-WAY 100135 by itself modified the acquisition of spatial learning. Administered into the dorsal hippocampus 15 min before each training session, (S)-WAY 100135 at doses of 0.2, 1 and 5 micrograms/microliters did not affect the acquisition of spatial learning but dose dependently prevented the impairment of choice accuracy caused by scopolamine, 3.75 micrograms/microliters infused into the same area. These findings suggest that blockade of 5-HT1A receptors can compensate the loss of cholinergic excitatory input on pyramidal cells, probably by favouring the action of other excitatory transmitters.