To our knowledge the intrahippocampal serotonergic 5-HT6 receptor tone on memory and amnesia models remains unexplored. Hence, in the present work we tested intrahippocampal administration of serotonin or 5-hydroxytryptamine (5-HT)6 receptor experimental molecules with differential intrinsic activity. Methods: In the present study, Automatized Autoshaping memory task was used, useful measuring memory, neural markers, and pharmacological effects. We are hypothesizing that experimental molecules with differential intrinsic activity might reveal serotonergic tone. Particularly, intrahippocampal administration of 5-HT6 receptor compounds with differential intrinsic activity (i.e., agonistic and antagonistic) might evidencing a serotonergic tone via this receptor. Bilateral intrahippocampal dose-response curves show that administration of EMD386088 (10 and 100 μg) had no effect or (50 μg) decreased conditioned responses (CR) in short- and long-term memory (STM and LTM, respectively); while SB-399885 (10 or 100 μg) significantly decreased CR in STM and LTM (24 and 48-h) or (50 μg) had no effect; thus suggesting that there is a 5-HT6 receptor tone regulating both STM and LTM. Moreover, intrahippocampal inactive doses of EMD386088 (5 μg) plus SB-399885 (0.5 μg) did not affect STM and LTM; however, partially or completely prevented the scopolamine or dizocilpine-induced amnesia. Thus confirming that both drugs exerted their effects through 5-HT6 receptor and that there is a hippocampal serotonergic tone under amnesic states, similar to that striatal.
