Effects of non-competitive AMPA receptor antagonists injected into some brain areas of WAG/Rij rats, an animal model of generalized absence epilepsy.

Abstract

CFM-2 [1-(4-aminophenyl)-3,5-dihydro-7,8-dimethoxy-4H-2,3-benzodiazepin-4-one] and THIQ-10c [N-acetyl-1-(4-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline], are two non-competitive 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionic acid (AMPA) receptor antagonists, which demonstrated to antagonize generalized tonic-clonic seizures in different animal models. We have evaluated the effects of such compounds in a genetic animal model of absence epilepsy, the WAG/Rij rat. Animals were focally microinjected into specific brain areas of the cortico-thalamic circuit in order to evaluate the effects of these compounds on the number and duration of epileptic spike-wave discharges (SWDs) and better characterize the role of AMPA neurotransmission in this animal model. The focal microinjection of the two AMPA antagonists into some thalamic nuclei (ventralis posteromedialis (VPM), reticularis (NRT), ventralis posterolateralis (VPL) and the primary somatosensory forelimb region (S1FL)) was, generally, not able to significantly modify the occurrence of SWDs. Whereas, both compounds were able to reduce the number and duration of SWDs dose-dependently when microinjected into the peri-oral region of the primary somatosensory cortex (S1po). These findings suggest that AMPA receptor antagonists might play a role in absence epilepsies and that it might depend on the involvement of specific neuronal areas.

• Authors: Rita Citraro, Emilio Russo, Santo Gratteri, Eugenio Donato Di Paola, Guido Ferreri Ibbadu, Carmela Curinga, Rosaria Gitto, Alba Chimirri, Giuseppe Donato, Giovambattista De Sarro
• Journal: Neuropharmacology (Neuropharmacology) Vol. 51 Issue 6 Pg. 1058-67 (Nov 2006) ISSN: 0028-3908 [Print] England
• PMID: 16901515 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticonvulsants
• Benzodiazepinones
• CFM 2
• Excitatory Amino Acid Antagonists
• Receptors, AMPA

Topics

• Animals
• Anticonvulsants
• Benzodiazepinones (administration & dosage, pharmacology)
• Brain (drug effects, physiology)
• Electrophysiology
• Epilepsy, Absence (drug therapy, physiopathology)
• Epilepsy, Generalized (drug therapy, physiopathology)
• Excitatory Amino Acid Antagonists (administration & dosage, pharmacology)
• Immunohistochemistry
• Male
• Microinjections
• Rats
• Rats, Inbred Strains
• Receptors, AMPA (antagonists & inhibitors)
• Somatosensory Cortex (physiopathology)
• Synaptic Transmission (drug effects)
• Thalamic Nuclei (drug effects, physiology)