Effects of non-competitive AMPA receptor antagonists injected into some brain areas of WAG/Rij rats, an animal model of generalized absence epilepsy.
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.
Citraro
Rita
R
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.
Russo
Emilio
E
Gratteri
Santo
S
Di Paola
Eugenio Donato
ED
Ibbadu
Guido Ferreri
GF
Curinga
Carmela
C
Gitto
Rosaria
R
Chimirri
Alba
A
Donato
Giuseppe
G
De Sarro
Giovambattista
G
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
D000927:Anticonvulsants; D001570:Benzodiazepinones; C119033:CFM 2; D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA