Epilepsy

CENTRAL NERVOUS SYSTEM

Porsolt offers models in all areas of psychopharmacology, epilepsy, sleep-wake, and neurodegenerative disorders. We are uniquely placed to offer a full range of CNS efficacy and safety pharmacology assessments, from basic models and regulatory tests, through the evaluation of abuse and dependence liability and proconvulsant risk using EEG.

Epilepsy

ACUTE EPILEPSY MODELS | Generalized seizures

> Electrical stimulation

Maximal Electroshock Test: tonic convulsions are induced by an electrical stimulation of high intensity.

Other test: Electroconvulsive Theshold Test (electrical stimulation of intermediate intensity)

TEST REFERENCE SPECIES ROUTE EFFECT
Maximal electroshock Carbamazepine Mouse/Rat p.o. ✔
Diazepam Mouse p.o., i.p. ✔
Lamotrigine Rat p.o. ✔
Valproate Rat i.p. ✔
Electroconvulsive shock threshold Diazepam Mouse/Rat p.o., i.p. ✔
Valproate Rat i.p. ✔

> Chemical substance

Pentylenetetrazol seizures test: Pentylenetetrazol administered subcutaneously, induces clonic and tonic convulsions in the mouse or in the rat.

Other substances can be used to induce convulsions (bicuculline, strychnine or picrotoxin).

TEST REFERENCE SPECIES ROUTE EFFECT
Pentylenetetrazol-induced convulsions Diazepam Mouse/Rat p.o., i.p. ✔
Valproate Rat i.p. ✔

ACUTE EPILEPSY MODELS | Partial seizures

> Electrical stimulation

6-Hz Psychomotor Test: electrical stimulation induces seizures characterized by forelimb clonus and Straub tail in the mouse.

CHRONIC EPILEPSY MODELS | Generalized seizure

> Genetic animal model

DBA/2 mice are susceptible to audiogenic seizures and exibit wild running followed by clonic and tonic convulsions when exposed to highintensity sound.

TEST REFERENCE SPECIES ROUTE EFFECT
Audiogenic seizure Carbamazepine Mouse p.o. ✔
Diazepam Mouse p.o., i.p. ✔
Lamotrigine Mouse p.o. ✔
Valproate Mouse i.p. ✔

CHRONIC EPILEPSY MODELS | Partial seizures

> Electrical stimulation

Electrical Amygdala Kindling test:  partial seizures with secondary generalization are induced by repeated electrical stimulation in a limbic region (amygdala for example).

TEST REFERENCE SPECIES ROUTE EFFECT
Electrical amygdala kindling Carbamazepine Rat p.o. ✔
Diazepam Rat p.o. ✔
Valproate Mouse i.p. ✔

> Parameters measured
     - Seizure score based on the Racine’s scale.
     - Afterdischarge duration evaluated by EEG recording.