Pharmacological characterization of phenytoin-resistant amygdala-kindled rats, a new model of drug-resistant partial epilepsy

The Anticonvulsant Response to Valproate in Kindled Rats Is Correlated with Its Effect on Neuronal Firing in the Substantia Nigra Pars Reticulata: A New Mechanism of Pharmacoresistance

“…Similar to phenytoin responders and nonresponders (Löscher et al, 1993), kindling development was not correlated to the later response to VPA in fully kindled rats. The only significant difference in kindling parameters was that the average postkindling control ADT was lower in good than poor VPA responders.…”

“…The only significant difference in kindling parameters was that the average postkindling control ADT was lower in good than poor VPA responders. Such a difference had previously also been observed in phenytoin responders versus nonresponders (Löscher et al, 1993) and, together with data from selective breeding of responders and nonresponders, had added to the hypothesis that the genetic background of an individual rat determines whether it becomes a responder or nonresponder to AEDs following the kindling process .…”

“…1), VPA was administered at a dose (200 mg/kg, i.p.) that had previously been shown to increase the ADT in kindled rats (Löscher et al, 1993), to enhance GABA turnover in the substantia nigra (Löscher, 1989), and to reduce single-unit firing in the SNr (Rohlfs et al, 1996). To Figure 1.…”

“…Pretreatment time (30 min) was chosen based on preliminary experiments and on previous studies in kindled rats (Löscher et al, 1993). In the preliminary experiments, we compared VPA plasma levels (see below) as well as the anticonvulsant efficacy (elevation of ADT) at time points of 15 and 30 min, respectively, after intraperitoneal injection of 200 mg/kg VPA.…”

“…Löscher et al (1993) showed that, in 80% of phenytoin nonresponders, VPA (200 mg/kg, i.p.) was also not efficient to increase ADTs.…”