Atorvastatin prevents development of kindling by modulating hippocampal levels of dopamine, glutamate, and GABA in mice

• Published in: Epilepsy & behavior 2015-01, Vol.42, p.48-53
• Main Authors: Sehar, Nouroz, Agarwal, Nidhi Bharal, Vohora, Divya, Raisuddin, S
• Format: Article
• Language: English
• Subjects: Animals; Anticonvulsants - therapeutic use; Atorvastatin; Atorvastatin Calcium; Dopamine; Dopamine - metabolism; Epilepsy; GABA; gamma-Aminobutyric Acid - drug effects; Glutamate; Glutamic Acid - metabolism; Heptanoic Acids - administration & dosage; Heptanoic Acids - pharmacology; Hippocampus - drug effects; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Kindling; Kindling, Neurologic - drug effects; Male; Mice; Neurology; Pyrroles - administration & dosage; Pyrroles - pharmacology; Seizures - prevention & control
• ISSN: 1525-5050; 1525-5069
• DOI: 10.1016/j.yebeh.2014.11.011

Abstract Purpose Atorvastatin (ATV) is widely used for the treatment of dyslipidemias. Recent evidence has shown that ATV has protection effects against seizures. However, the effect of ATV on certain neurotransmitter and oxidative stress markers associated with seizures had not been reported. Therefore, the present study aimed to evaluate the effects of ATV on oxidative stress markers on whole brain and GABA, glutamate, and dopamine levels in the hippocampus of PTZ-kindled mice. Additionally, effects of ATV on animal models of seizures, anxiety, and depression were also assessed. Materials and methods Swiss albino mice were given ATV (20, 40, and 80 mg/kg/p.o.) in an acute study. On the seventh day, animals were subjected to various neurological and neurobehavioral tests, viz, increasing current electroshock (ICES) test, pentylenetetrazole (PTZ)-induced seizures, Elevated Plus Maze (EPM), and Forced Swim Test (FST). For the development of kindling, a subconvulsant dose of PTZ, i.e., 25 mg/kg, i.p., was administered every other day, and ATV in all the three doses was administered daily. Seizure score was continuously monitored until the development of kindling. Thiobarbituric acid reacting species (TBARS), glutathione, dopamine, GABA, and glutamate levels were also assessed in the brain tissues of mice. Results The results showed that in the ICES test, ATV 80 mg/kg increased the seizure threshold to hind limb extension (HLE), and a complete protection against HLE was observed when ATV 80 mg/kg was combined with a subanticonvulsant dose of phenytoin. Atorvastatin in all the tested doses suppressed the development of kindling, reduced lipid peroxidation, and increased glutathione levels. All doses of ATV maintained the normal levels of glutamate, GABA, and dopamine in kindled mice. Conclusion Atorvastatin possesses anticonvulsant activity against electroconvulsions. It was found to suppress the development of PTZ kindling, presumably altering the redox status and hippocampal levels of dopamine, glutamate, and GABA.