Suppression of memory acquisition due to co-administration of lithium and atorvastatin in male mice: Role of nitric oxide pathway

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Event Abstract Back to Event Suppression of memory acquisition due to co-administration of lithium and atorvastatin in male mice: Role of nitric oxide pathway Mehrak Javadi-Paydar1*, Amir Reza Honarmand2, Nasim Pourtabatabaei2 and Ahmad Reza Dehpour1 1 Tehran University of Medical Sciences, Department of Pharmacology, School of Medicine, Iran 2 Tehran University of Medical Sciences, Brain and Spinal Cord Injury Repair Research Center, Iran Background and Aim: Lithium, a widely used drug in bipolar-affective disorders, plays a controversial role in memory and cognitive function. The effectsof lithium is shown to be mediated through nitric oxide (NO), which also regulates cognitive performance. On the other hand, atorvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, influenced the memory performance through NO pathway. The aim of this study was to investigate the interacting effect of lithium and atorvastatin on cognitive performance and to investigate the role of NO as a potential mechanism involved in this interaction to have an improving effect on cognition. Material and methods. Memory performance was evaluated in a two-trial recognition Y-maze test and passive avoidance in mice. Lithium (5, 10, 20 or 40 mg/kg, i.p.) and atorvastatin (1 mg/kg, p.o.), was administered 1 hours before each trial, L-NAME, a non-specific NO synthase inhibitor (3, 10 mg/kg, i.p.); L-arginine, a NO precursor (750mg/kg) administered 30 minutes before training sessions. Results. 1) Lithium (40 mg/kg) impaired the acquisition of recognition spatial memory; 2) Lithium did not affect the retrieval phase of spatial memory; 3) Atorvastatin (1 mg/kg), significantly impaired the memory performance, when co-administered with the sub-effective dose of lithium (10 mg/kg), but did not affect the status when administered with lithium (5 mg/kg); 4) L-NAME (10 mg/kg) dramatically decreased memory performance in mice received subeffective doses of both lithium (5 mg/kg) and atorvastatin (1 mg/kg); 5) L-arginine (750 mg/kg) improved the memory acquisition in mice administered lithium (10 mg/kg) and atorvastatin (1 mg/kg); 6) Lithium did not affect the cognitive performance in the passive avoidance test. Discussion: Atorvastatin remarkably deteriorates the memory impairing effect of lithium, and this effect is highly dependant to the dose of lithium. Inhibition of NO synthesis with L-NAME aggravated memory impairment of lithium and atorvastatin co-administraion; reversely, L-arginine improved this effect. In conclusion, the present study suggests that nitrergic pathway is involved in the improvement of memory devastation induced by coadministration of lithium and atorvastaitn.