title: 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.affiliation: Section of Pharmacology, Department of Experimental and Clinical Medicine, Faculty of Medicine and Surgery, University of Catanzaro, School of Medicine at Catanzaro, Policlinico Mater Domini, Via Tommaso Campanella, 115, 88100 Catanzaro, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Citraro
authors.forename: Emilio
authors.initials: E
authors.lastname: Russo
authors.forename: Santo
authors.initials: S
authors.lastname: Gratteri
authors.forename: Eugenio Donato
authors.initials: ED
authors.lastname: Di Paola
authors.forename: Guido Ferreri
authors.initials: GF
authors.lastname: Ibbadu
authors.forename: Carmela
authors.initials: C
authors.lastname: Curinga
authors.forename: Rosaria
authors.initials: R
authors.lastname: Gitto
authors.forename: Alba
authors.initials: A
authors.lastname: Chimirri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Donato
authors.forename: Giovambattista
authors.initials: G
authors.lastname: De Sarro
mesh_terms: D000818:Animals; D000927:Anticonvulsants; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D004594:Electrophysiology; D004832:Epilepsy, Absence / Q000188:drug therapy / Q000503:physiopathology*; D004829:Epilepsy, Generalized / Q000188:drug therapy / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D008845:Microinjections; D051381:Rats; D011919:Rats, Inbred Strains; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D013003:Somatosensory Cortex / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects; D013787:Thalamic Nuclei / Q000187:drug effects / Q000502:physiology
chemical_list: D000927:Anticonvulsants; D001570:Benzodiazepinones; C119033:CFM 2; D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA