Systemic (IP) and/or intraseptal (IS) administration of scopolamine (SCP) and diazepam (DZP) induce amnesia, whereas IP injection of the neuropeptide substance P (SP) and choline chloride (ChCl) produce memory facilitation. The septohippocampal cholinergic system has been pointed out as a possible site of SCP and DZP-induced amnesia as well as for the mnemonic effects induced by SP and ChCl. We performed a series of experiments in order to investigate the interactions between cholinergic and GABA/benzodiazepine (GABA/BZD) systems with the SPergic system on inhibitory avoidance retention. Male Wistar rats were trained and tested in a step-down inhibitory avoidance task (1.0 mA footshock). Animals received, pre-training, IP (1.0 mg/kg) or IS (1.0 nM/0.5 microl) injection of DZP, SCP (SCP; 1.0 mg/kg - IP or 0.5 microM/0.5 microl--IS) or vehicle (VEH). Immediately after training they received an IP or IS injections of SP 1-11 (50 microg/kg--IP or 1.0 nM/0.5 microl--IS), SP 1-7 (167 microg/kg--IP or 1.0 nM/0.5 microl--IS), ChCl (20 mg/kg--IP or 0.3 microM/0.5 microl--IS) or VEH. Rats pretreated with SCP and DZP showed amnesia. Post-trial treatments with SP 1-11, SP 1-7 or ChCl blocked the amnesic effects of SCP and DZP. These findings suggest an interaction between SPergic and cholinergic mechanisms with GABAergic systems in the modulation of inhibitory avoidance retention and that the effects of these treatments are mediated, at least in part, by interactions in the septohippocampal pathway.
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