STIMULATION OF 5-HT1A RECEPTORS IN THE DORSAL RAPHE REVERSES THE IMPAIRMENT OF SPATIAL-LEARNING CAUSED BY INTRAHIPPOCAMPAL SCOPOLAMINE IN RATS

This study investigated the effect of stimulating 5-HT1A receptors in the dorsal raphe on the impairment of learning caused by 4 mu g/mu L s copolamine injected in the CA1 region of the dorsal hippocampus in rat s performing a two-platform spatial discrimination task, At 1 (but not 0.2) mu g/0.5 mu L administered in the dorsal raphe on each acquisiti on training day 5 min before bilateral intrahippocampal injection of 4 mu g/mu L scopolamine, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH- DPAT), a 5-HT1A receptor agonist, had no effect on choice accuracy and latency or errors of omission but completely antagonized the impairme nt of choice accuracy by intrahippocampal scopolamine. Administered in to the dorsal raphe at 0.2 and 1 mu g/0.5 mu L, WAY 100635, a 5-HT1A r eceptor antagonist, had no effect on rats' performance or on the impai rment caused by intrahippocampal scopolamine but dose-dependently anta gonized the effect of 1 mu g/0.5 mu L 8-OH-DPAT on the scopolamine-ind uced deficit. The results show that stimulation of presynaptic 5-HT1A, receptors in the dorsal raphe reverses the deficit caused by intrahip pocampal scopolamine, probably by facilitating the transfer of facilit atory information from the entorhinal cortex to the hippocampus. Toget her with a previous study showing that blockade of postsynaptic hippoc ampal 5-HT1A receptors antagonized the effect of intrahippocampal scop olamine in the two-platform spatial discrimination task (Carli et al., 1995b), the results suggest that drugs with presynaptic stimulatory a nd postsynaptic blocking actions on 5-HT1A receptors, such as partial agonists at these receptors, may be useful in the symptomatic treatmen t of human memory disturbances associated with loss of cholinergic inn ervation to the hippocampus.