Adjuvant effects of classical music on simvastatin induced reduction of anxiety but not object recognition memory in rats.

Abstract

Simvastatin is one of many hydroxymethylglutaryl-coenzyme-A reductase inhibitors that are prescribed to lower cholesterol. Some emerging evidence indicates that classical music can serve as an effective adjuvant in rats treated with simvastatin. Moreover, simvastatin and classical music have been shown to influence some cognitive functions. To further understand the mechanisms of action, we exposed rats to classical music for 1 month, and then treated them orally with simvastatin. The behavioral experiments suggested that exposure to subchronic simvastatin (1 or 10 mg/kg/day) reduced anxiety levels in the elevated plus-maze and open-field test in rats exposed to Mozart music. The recognition object test results indicated that simvastatin altered non-spatial working memory only at the 1 mg/kg/day dose and improved both short-and long-term object recognition. No significant differences were found between Mozart music and silence in the object recognition test, suggesting that music did not significant affect learning and memory in adult rats. We hypothesize that the anxiolytic, but not object-recognition memory, effects of simvastatin and classical music occur through similar mechanisms, providing an important foundation for future preclinical and clinical research.

Simvastatin treatment reduces the cholesterol content of membrane/lipid rafts, implicating the N -methyl-D-aspartate receptor in anxiety: a literature review

“…Reduction of the availability of NMDA receptors to interact with NMDA or its physiological ligand glutamate is one mechanism that might mediate the anxiolytic activity of SIM. Our results also provide strong evidence that chronic high-dose SIM administration has NMDA antagonist-like effects, which would partially explain the anxiolytic effects of this drug (Camargo et al, 2013;Carrocini et al, 2012;Cruz et al, 2011;Pauleti et al, 2013;Santos et al, 2012).…”

“…It is well documented that NMDA receptors in the brain have a close correlation with anxiety-like activity (Bergink, van Megen, Westenberg, 2004;ChojnackaWójcik, Kłodzinska, Pilc, 2001). Modulation of NMDA receptors activity after SIM treatment could explain the drug's anxiolytic-like effects (Camargo et al, 2013;Carrocini et al, 2012;Cruz et al, 2011;Kilic et al, 2012;Pauleti et al, 2013;Santos et al, 2012;Wang et al, 2009;Yan et al, 2011). This hypothesis could be supported by the fact that altered levels of NMDA receptors in the hippocampus and amygdala directly influence anxiety behaviors (Barkus et al, 2010;Blundell, Adamec, 2007;Masneuf et al, 2014).…”

“…Additionally, chronic SIM treatment in rats stimulates the production of brain-derived neurotrophic factor in the hippocampus after traumatic brain injury by activating Akt-mediated signaling (Wu et al, 2008), as well as increases NMDA receptor levels, promotes neurogenesis, and increases cerebral blood flow by up-regulating vascular growth factor, synaptophysin, Akt, and ERK (Chen et al, 2003;Wang et al, 2009). However, numerous pre-clinical studies led to the hypothesis that hypofunctional NMDA receptors may also play an important role in the mechanism of anxiolytic actions after SIM treatment (Camargo et al, 2013;Carrocini et al, 2012;Cruz et al, 2011;Pauleti et al, 2013;Santos et al, 2012;Wang et al, 2009;Yan et al, 2011). Accordingly, the functional consequence of such regulation on NMDA receptor function varies on the basis of both the identity of the G protein coupled receptor, and the cell type in which relevant receptors are expressed.…”

Antioxidant effect of simvastatin throught oxidative imbalance caused by lisdexamfetamine dimesylate

“…During the light and dark phases, the rats were exposed to light intensities of approximately 325 and 0.025 lux, respectively. These lux values were chosen because they were the light (Santos et al 2012, Camargo et al 2013). …”

“…Current studies on the applications of statins have demonstrated their neuroprotective and clinical signifi cance among neurodegenerative diseases like cerebral ischemic stroke, vascular dementia, Alzheimer's disease, and Parkinson's disease, though the neuroprotective mechanisms are not completely understood (Vance 2012, Barone et al 2014, Moon et al 2014). There is a growing recognition that statins have pleiotropic effects beyond lowering cholesterol levels (Santos et al 2012, Camargo et al 2013.…”