Possible interaction of cholinergic and GABAergic systems between MS and CA1 upon memory acquisition in rats

► Intra-CA1/septum injection of scopolamine and muscimol decreased memory acquisition. ► Physostigmine and bicuculline increased memory acquisition into CA1/septum. ► Muscimol increased memory impairment induced by scopolamine in the septum/CA1. ► Bicuculline decreased memory impairment induced by scopolamine in the septum/CA1. ► Bicuculline did not alter memory improvement induced by physostigmine. The present study explored the possibility that cholinergic and GABAergic systems of medial septum (MS) might influence acquisition of memory by regulation of acetylcholine (Ach) and γ-aminobutyric acid (GABA) receptors function in hippocampus and vice versa. The step-through passive avoidance (PA) task was used. The results showed that pre-training intra-MS/CA1 administration of nonselective muscarinic Ach antagonist, scopolamine (0.5, 1 and 2μg/rat) and GABAA receptor agonist, muscimol (0.01 and 0.02μg/rat) impaired, while acetylcholinesterase inhibitor, physostigmine (0.5 and 1μg/rat) and GABAA receptor antagonist, bicuculline (0.25μg/rat) improved memory acquisition. Moreover, intra-CA1/MS administration of a subthreshold dose of muscimol or bicuculline increased and reversed the impairment induced by scopolamine in MS/CA1 respectively (cross injection). Also, the result revealed that, intra-CA1/MS administration subthreshold dose of muscimol reduced improvement of memory induced by physostigmine in the MS/CA1, respectively (cross injection). On the other hand, subthreshold dose of bicuculline in CA1/MS did not alter memory improvement induced by physostigmine in the other site (MS/CA1). In conclusion, both cholinergic and GABAergic systems not only seem to play a role in the modulation of memory in the MS and CA1 but also to have a complex interaction.