Potentiation of mGlu5 receptors with the novel enhancer, VU0360172, reduces spontaneous absence seizures in WAG/Rij rats

Autor: E.L.J.M. van Luijtelaar, Shaun R. Stauffer, A. Prete, Ya Zhou, Francesca Biagioni, Craig W. Lindsley, Paige N. Vinson, Gemma Molinaro, Carrie K. Jones, C.M. van Rijn, P.J. Conn, F. Nicoletti, Richard Teke Ngomba, Ines Santolini, Alice L. Rodriguez, V. D'Amore
Rok vydání: 2013
Předmět:
Male
Niacinamide
medicine.medical_specialty
Pyridines
Receptor
Metabotropic Glutamate 5
Stimulation
Motor Activity
Somatosensory system
Biologische psychologie
Receptors
Metabotropic Glutamate
vu0360172
Article
Cellular and Molecular Neuroscience
Phosphatidylinositol Phosphates
Internal medicine
medicine
Excitatory Amino Acid Agonists
Animals
Receptor
mtep
Pharmacology
Cerebral Cortex
Ventral Thalamic Nuclei
absence epilepsy
mglu5 receptor
wag/rij rats
Chemistry
Hydrolysis
Glutamate receptor
Age Factors
Long-term potentiation
Electroencephalography
Rats
Inbred Strains
Plasticity and Memory [DI-BCB_DCC_Theme 3]
Somatosensory Cortex
Brain Waves
Rats
Disease Models
Animal
Thiazoles
MTEP
Endocrinology
Metabotropic receptor
Epilepsy
Absence
Metabotropic glutamate receptor
Biological psychology
Neuroscience
Excitatory Amino Acid Antagonists
Zdroj: Neuropharmacology, 66, 330-338
Neuropharmacology, 66, pp. 330-338
ISSN: 0028-3908
DOI: 10.1016/j.neuropharm.2012.05.044
Popis: Absence epilepsy is generated by the cortico-thalamo-cortical network, which undergoes a finely tuned regulation by metabotropic glutamate (mGlu) receptors. We have shown previously that potentiation of mGlu1 receptors reduces spontaneous occurring spike and wave discharges (SWDs) in the WAG/Rij rat model of absence epilepsy, whereas activation of mGlu2/3 and mGlu4 receptors produces the opposite effect. Here, we have extended the study to mGlu5 receptors, which are known to be highly expressed within the cortico-thalamo-cortical network. We used presymptomatic and symptomatic WAG/Rij rats and aged-matched ACI rats. WAG/Rij rats showed a reduction in the mGlu5 receptor protein levels and in the mGlu5-receptor mediated stimulation of polyphosphoinositide hydrolysis in the ventrobasal thalamus, whereas the expression of mGlu5 receptors was increased in the somatosensory cortex. Interestingly, these changes preceded the onset of the epileptic phenotype, being already visible in pre-symptomatic WAG/Rij rats. SWDs in symptomatic WAG/Rij rats were not influenced by pharmacological blockade of mGlu5 receptors with MTEP (10 or 30 mg/kg, i.p.), but were significantly decreased by mGlu5 receptor potentiation with the novel enhancer, VU0360172 (3 or 10 mg/kg, s.c.), without affecting motor behaviour. The effect of VU0360172 was prevented by co-treatment with MTEP. These findings suggest that changes in mGlu5 receptors might lie at the core of the absence-seizure prone phenotype of WAG/Rij rats, and that mGlu5 receptor enhancers are potential candidates to the treatment of absence epilepsy. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'.
Databáze: OpenAIRE
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