The role of nitric oxide in spatial memory stages, hippocampal ERK and CaMKII phosphorylation

•L-NAME impairs memory acquisition, consolidation and retrieval.•Memory formation induces hippocampal ERK and CaMKII phosphorylation.•L-NAME inhibits hippocampal ERK and CaMKII phosphorylation.

Nitric oxide (NO) is an important intercellular messenger in the control of physiologic functions. It is synthesized by 3 different nitric oxide synthase enzymes (NOS). Uses of non-selective NOS inhibitor (L-NAME) have shown that NO is involved in neuronal plasticity and memory. This study aimed to determine the differential role of NO in spatial memory formation steps. In addition, regarding the roles of ERK and CaMKII in hippocampal plasticity, the hippocampal ERK and CaMKII activities were assessed to identify the effect of L-NAME on those proteins during each phase of memory.Adult male Sprague–Dawely rats weighing 220–280 g were trained in a single session consisting of 8 trials. To evaluate the effect of L-NAME on acquisition, L-NAME (3 or 10 mg/kg/i.p.) was administered 30 min before training. To assess its effect on the consolidation phase, L-NAME (3 or 10 mg/kg/i.p.) was injected immediately after training and a probe test was carried out 24 h later to analyse memory retention. To determine its effect on memory retrieval L-NAME (3 or 10 mg/kg/i.p.) was injected 30 min before probe trial which was conducted 24 h after training. The hippocampi were isolated after behavioural studies and western blotting analysis on hippocampal lysates was performed to illustrate the levels of phosphorylated ERK and CaMKII. The results showed that pre-training administration of L-NAME in 10 mg/kg but not 3 mg/kg deteriorates acquisition. Post-training and pre-probe administration of L-NAME in 10 mg/kg but not 3 mg/kg impaired animal's performance in probe test. Additionally L-NAME treatment decreased the amount of phosphorylated (activated) ERK and CaMKII in the hippocampus. This study showed that endogenous nitric oxide is involved not only in all stages of memory, but also in ERK and CaMKII activation in the hippocampus during all 3 stages of memory.