The effect of prolonged simvastatin application on serotonin uptake, membrane microviscosity and behavioral changes in the animal model
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
26917054
DOI
10.1016/j.physbeh.2016.02.029
PII: S0031-9384(16)30073-7
Knihovny.cz E-zdroje
- Klíčová slova
- Behavior, Brain, Cholesterol, Rats, Serotonergic neurotransmission, Statins,
- MeSH
- anticholesteremika farmakologie MeSH
- bludiště - učení účinky léků MeSH
- časové faktory MeSH
- cholesterol metabolismus MeSH
- chování zvířat účinky léků MeSH
- erytrocyty účinky léků MeSH
- fluorescenční polarizace MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
- krevní plazma účinky léků MeSH
- krysa rodu Rattus MeSH
- modely u zvířat MeSH
- mozek účinky léků MeSH
- neparametrická statistika MeSH
- pátrací chování účinky léků MeSH
- potkani Long-Evans MeSH
- serotonin metabolismus MeSH
- simvastatin farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- anticholesteremika MeSH
- cholesterol MeSH
- serotonin MeSH
- simvastatin MeSH
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 (30mg/kg per day) for 2 or 4weeks. 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.
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