title: Atorvastatin prevents development of kindling by modulating hippocampal levels of dopamine, glutamate, and GABA in mice.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Swiss albino mice were given ATV (20, 40, and 80mg/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., 25mg/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 80mg/kg increased the seizure threshold to hind limb extension (HLE), and a complete protection against HLE was observed when ATV 80mg/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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre for Translational and Clinical Research, Jamia Hamdard, New Delhi 110062, India; Department of Medical Elementology and Toxicology, Jamia Hamdard, New Delhi 110062, India. Electronic address: nouroz_sehar@yahoo.com.
authors.forename: Nouroz
authors.initials: N
authors.lastname: Sehar
authors.affiliation: Centre for Translational and Clinical Research, Jamia Hamdard, New Delhi 110062, India. Electronic address: nidhi.bharal@gmail.com.
authors.forename: Nidhi Bharal
authors.initials: NB
authors.lastname: Agarwal
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India. Electronic address: divyavohora@hotmail.com.
authors.forename: Divya
authors.initials: D
authors.lastname: Vohora
authors.affiliation: Centre for Translational and Clinical Research, Jamia Hamdard, New Delhi 110062, India; Department of Medical Elementology and Toxicology, Jamia Hamdard, New Delhi 110062, India. Electronic address: sraisuddin@jamiahamdard.ac.in.
authors.forename: S
authors.initials: S
authors.lastname: Raisuddin
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D000069059:Atorvastatin; D004298:Dopamine / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D051379:Mice; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D012640:Seizures / Q000517:prevention & control*; D005680:gamma-Aminobutyric Acid / Q000187:drug effects*
chemical_list: D000927:Anticonvulsants; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000069059:Atorvastatin; D004298:Dopamine
keywords: Atorvastatin; Dopamine; Epilepsy; GABA; Glutamate; Kindling