Behavioral interactions of simvastatin and fluoxetine in tests of anxiety and depression

Tainaê Santos,¹ Monaliza Marizete Baungratz,¹ Suellen Priscila Haskel,² Daniela Delwing de Lima,³ Júlia Niehues da Cruz,⁴ Débora Delwing Dal Magro,⁵ José Geraldo Pereira da Cruz<sup>5

1</sup>Department of Medicine, ²Department of Physiotherapy, Regional University of Blumenau, Santa Catarina, Brazil; ³Department of Pharmacy, University of Joinville Region, Santa Catarina, Brazil; ⁴Department of Medicine, University of the Extreme South of Santa Catarina, Santa Catarina, Brazil; ⁵Department of Natural Sciences, Regional University of Blumenau, Santa Catarina, Brazil


Abstract: Simvastatin inhibits 3-hydroxy-3-methylglutaryl CoA reductase, the rate-limiting enzyme in the cholesterol biosynthetic pathway, and is widely used to control plasma cholesterol levels and prevent cardiovascular disease. However, emerging evidence indicates that the beneficial effects of simvastatin extend to the central nervous system. The effects of simvastatin combined with fluoxetine provide an exciting and potential paradigm to decreased anxiety and depression. Thus, the present paper investigates the possibility of synergistic interactions between simvastatin and fluoxetine in models of anxiety and depression. We investigated the effects of subchronically administered simvastatin (1 or 10 mg/kg/day) combined with fluoxetine (2 or 10 mg/kg) at 24, 5, and 1 hour on adult rats before conducting behavioral tests. The results indicate that simvastatin and/or fluoxetine treatment reduces anxiety-like behaviors in the elevated plus-maze and open-field tests. Our results showed that simvastatin and/or fluoxetine induced a significant increase in the swimming activity during the forced swimming test (antidepressant effect), with a concomitant increase in climbing time in simvastatin-treated animals only (noradrenergic activation). We hypothesize that anxiolytic and antidepressant effects of simvastatin and/or fluoxetine produce their behavioral effects through similar mechanisms and provide an important foundation for future preclinical research.

Keywords: elevated plus-maze, fluoxetine, forced swimming test, open-field, simvastatin