Tabriz University of Medical Sciences Medical Journal of Tabriz University of Medical Sciences 2783-2031 34 5 2013 01 28 Counteraction Effect of Endogenous Serotonin and Cyclic Guanosine Mono Phosphate on the Anxiety Level in Mice 41 45 EN Siamak Shahidi Nasrin Hashemi-Firouzi Minoo Mahmoodi Journal Article 2013 01 28 Background and Objectives: Selective serotonin reuptake inhibitors are widely used as anti-depressant but some adverse effects such as anxiety and sexual dysfunction have been reported. On the other hand, the effect of sildenafil, a phosphodiesterase inhibitor, which increase nitric oxide on the anxiety is controversial and there is an interaction between serotonergic systems with NO-cGMP pathway. The aim of this study was to evaluate the synergic effects of co-administration of fluoxetine and sildenafil on anxiety. Materials and Methods: In this experimental study, investigated on male mice (20-35 g) into control and experimental groups. The experimental groups received fluoxetine (20, 10 and 5 mg/kg), or a combination of fluoxetine (20, 10 and 5 mg/kg) sildenafil (10, 2 and 1 mg/kg) control group saline was injected intraperitoneally (i.p.) fifteen minutes prior placing in the Elevated plus-maze. The time spent in the open arms, number of entries in the open arms and number of total entries into the arms was measured. Results: Administration of fluoxetine decreased the time spent and number of entries into the open arms. There is no significant difference in those measurable variables in co-administration of fluoxetine and sildenafil compared with control group. Conclusion: Co-administration of fluoxetine and sildenafil has no therapeutic effect on anxiety. It seems that co-administration of sildenafil decreases the anxieogenic effect of fluoxetine.