S 15535, a benzodioxopiperazine acting as presynaptic agonist and postsynaptic 5-HT1A receptor antagonist, prevents the impairment of spatial learning caused by intrahippocampal scopolamine

1 The effect of S 15535 (4-benzodioxan-5-yl) 1-(indan-2-yl)piperazine), an agonist at presynaptic and antagonist at postsynaptic 5-HT1A receptors, on the impairment of spatial learning caused by intrahippocampal scopolamine i n a two-platform spatial discrimination task was studied. 2 Scopolamine (4.0 mu g mu l(-1)), injected bilaterally into the CA1 region of the dorsal hippocampus 10 min before each training session, impaired ch oice accuracy with no effect on choice latency and errors of omission. 3 Administered subcutaneously 30 min before each training session, S 15535 1.0 (but not 0.3) mg kg(-1) did not modify choice accuracy but prevented it s impairment by intrahippocampal scopolamine. 4 WAY 100635, a 5-HT1A receptor antagonist, injected into the dorsal raphe at 1.0 mu g 0.5 mu l(-1) 5 min before scopolamine, had no effect on choice accuracy and latency or errors of omission and did not modify the effect of scopolamine but completely antagonized the effect of S 15535 (1.0 mg kg(-1 )) on scopolamine-induced impairment of choice accuracy. 5 The results confirm a previous report (Carli et al., 1998) that stimulati on of presynaptic 5-HT1A receptors in the dorsal raphe counteracts the defi cit caused by intrahippocampal scopolamine, probably by facilitating the tr ansfer of facilitatory information from the entorhinal cortex to the hippoc ampus. 6 Drugs that stimulate action on presynaptic 5-HT1A receptors, such as S 15 535 and other partial 5-HT1A receptors agonists, may be useful in the sympt omatic treatment of human memory disturbances associated with loss of choli nergic innervation to the hippocampus.