Scopolamine- and diazepam-induced amnesia are blocked by systemic and intraseptal administration of substance P and choline chloride

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 μl) injection of DZP, SCP (SCP; 1.0 mg/kg – IP or 0.5 μM/0.5 μl – IS) or vehicle (VEH). Immediately after training they received an IP or IS injections of SP 1-11 (50 μg/kg – IP or 1.0 nM/0.5 μl – IS), SP 1-7 (167 μg/kg – IP or 1.0 nM/0.5 μl – IS), ChCl (20 mg/kg – IP or 0.3 μM/0.5 μl – 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.

Research highlights▶ This study investigates interactions between cholinergic and GABA/benzodiazepine systems with the substance P system on inhibitory avoidance retention in rats. We find that post-trial treatment with substance P or choline chloride blocks the amnesic effects of diazepam and the cholinergic antagonist scopolamine. ▶ The results of this study clearly indicate interactions between the substance P and cholinergic systems with GABAergic system in the modulation of inhibitory avoidance retention. Moreover, considering the pharmacological responses of our set-up, the effects of the treatments described in the paper seems to be mediated, at least in part, by interactions involving the septohippocampal pathway.