Journal
PHYSIOLOGY & BEHAVIOR
Volume 158, Issue -, Pages 112-120Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.physbeh.2016.02.029
Keywords
Statins; Rats; Cholesterol; Brain; Serotonergic neurotransmission; Behavior
Categories
Funding
- Charles University in Prague, Czech Republic [PRVOUK-P26/LF1/4, P34]
- GAUK [392015]
- IGA MZ CR [NT/1448, NT13403-4/2012]
- GACR [P304/12/G069, P303/12/1464, SW 260256/2016]
- project National Institute of Mental Health (NIMH-CZ) [ED2.1.00/03.0078]
- European Regional Development Fund
- project Sustainability for the National Institute of Mental Health [LO1611]
- Ministry of Education, Youth and Sports of the Czech Republic
- AV CR [M200111204]
- EU structural funds - Operational Programme Prague - Competitiveness [CZ.2.16/3.1.00/22197]
- Ministry of Education, Youth and Sports Czech Republic in the National Programme of Sustainability I - NPU I (LO) [MSMT-34807/2013, MSM/LH12116]
- [RVO: 67985823]
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Simvastatin and other statins (HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitors) are extensively used in clinical practices and are very effective in decreasing serum low-density lipoprotein cholesterol. However, their effect on cholesterol synthesis in central nervous system and its behavioral consequences have not been fully understood yet. We have studied selected biologic traits potentially affected by statin treatment serotonin (5-HT) uptake in platelets, membrane microviscosity in erythrocytes, cholesterol level in the brain (amygdala; hippocampus and prefrontal cortex), as well as behavioral changes in an elevated plus maze and open field test in male Long-Evans rats, which were treated by simvastatin (30 mg/kg per day) for 2 or 4 weeks. We demonstrated: 1) a decrease in both serotonin transporter (SERT) activity and membrane microviscosity after treatment with simvastatin, 2) lower cholesterol content in all tested brain regions in animals from the simvastatin treated group, and 3) longer time spent in the open arms and a higher number of entrances to the closed arms in the elevated plus maze by animals from the simvastatin group compared to animals from the control group, but no differences in behavior in the open field test. Taken together, our results confirmed complex alterations, including behavioral changes, after the cholesterol lowering treatment. Furthermore, we discuss the possibility that the behavioral changes, traditionally interpreted as an anxiolytic effect, may be interpreted as increased impulsivity. We also confirmed that such behavioral changes may be attributed to changes in serotonergic neurotransmission. (C) 2016 Elsevier Inc. All rights reserved.
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