Anticonvulsant Effect of (RS)-1-Aminoindan-1,5-dicarboxylic Acid on Pentetrazol-Induced Kindled Seizures in Mice

Abstract

The present study was undertaken to clarify the effect of group I metabotropic glutamate receptor (mGluR) antagonist, (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) on pentetrazol-induced kindled seizures. The mechanism of the anticonvulsant effect of AIDA was also studied. Mice were anesthetized with pentobarbital; the electrodes and guide cannula were chronically implanted into the cortex and lateral ventricle. In order to induce kindling, pentetrazol at a dose of 40 mg/kg was injected intraperitoneally once every 48 h. Behavioral and electroencephalographic (EEG) seizures were observed for 20 min following pentetrazol administration. Intracerebroventricular (i.c.v.) injection of AIDA (1000 nmol/site) resulted in a significant inhibitory effect on pentetrazol-induced kindled seizures, and this effect was antagonized by a group I mGluR agonist, (RS)-3,5-dihydroxyphenylglycine ((RS)-3,5-DHPG). The effect of AIDA (200 nmol/site) on pentetrazol-induced kindled seizures was augmented by the simultaneous use of g g-aminobutyric acid (GABA) mimetic drugs, such as NNC-711 and diazepam. Moreover, the effect of AIDA (1000 nmol/site) on pentetrazol-induced kindled seizures was antagonized by a GABA A receptor antagonist, bicuculline and a GABA C receptor antagonist, (1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA). It can be concluded that AIDA had an anticonvulsant effect on pentetrazol-induced kindled seizures, which was partially mediated by the GABAergic mechanism through GABA A and GABA C receptors.

Mice Heterozygous for the Oxytocin Receptor Gene (Oxtr+/−) Show Impaired Social Behaviour but not Increased Aggression or Cognitive Inflexibility: Evidence of a Selective Haploinsufficiency Gene Effect

“…Eleven‐week‐old Oxtr +/+ , Oxtr +/ − and Oxtr − / − mice were anaesthetised with chloral hydrate (450 mg/kg i.p. ; Sigma‐Aldrich, St Louis, MO, USA) and a guide cannula was implanted into the right lateral ventricle as described previously following the coordinates of Franklin and Paxinos (from bregma = anteroposterior −0.1 mm; mediolateral + 0.9 mm; and dorsoventral + 3.0 mm). The guide cannula, equipped with a membrane to avoid fluid reflux, was firmly attached to the skull using a mounting screw (Plastics One Inc., Wallingford, CT, USA) and dental cement (Palavit; New Galetti Rossi, Milan, Italy).…”

Emerging roles of Na+/H+ exchangers in epilepsy and developmental brain disorders

“…Their ability to induce more dramatic Cl – currents than benzodiazapines and to increase propensity for side effects makes the barbiturates a second-line choice for epilepsy treatment (Loscher and Rogawski, 2012). Of note, the closely related GABA A -ρ receptor, formerly known as GABA c receptor, is insensitive to both barbiturates and benzodiazepines and has a less clear role in epilepsy (Johnston, 1996; Watanabe et al, 2010). …”