Objective: 

As an important member of the statin family, simvastatin has been shown to increase nitric oxide (NO) levels in several studies. NO is a widespread and multifunctional biological messenger molecule in mammals. In this study, altered anxiety levels by simvastatin administration have been investigated to determine whether the NO mediated mechanisms are involved in this effect.

Methods: 

Seven groups of animals, each consisting of 8 Sprague Dawley rats were tested by elevated plus maze (EPM) and open field margin time (OFMT) methods, to observe anxiety levels. When vehicle group was administered with phosphate buffered saline (PBS) alone, two groups were administered 20 or 40 mg/kg simvastatin + PBS and the other groups were administered simvastatin + L-NAME of 10 or 50 mg/kg. All groups were tested in the 1st, 4th, 7th, 10th, 15th, 21th and 28th days of vehicle or drug administration.The effects of different doses of simvastatin and L-NAME application on EPM and OFMT tests in rats were analyzed using two way analizes of variances.

Results: 

Results are shown that, 40mg/kg simvastatin only group EPM times spent in the close arms were significantly higher than the vehicle group (p <0. 05). Also, 20 and 40 mg/kg simvastatin only groups had higher OFMT when compared to vehicle group (p < 0.05). The higher observed time spent in closed arms in EPM and OFMT are considered as anxiogenic-like behavior.

Conclusions: 

The results suggested that anxiogenic like behavior caused by simvastatin administration was inhibited with L-NAME administration. Thus, these results indicate that anxiogenic like behavior caused by simvastatin administration is modulated by an NO-involved mechanism.