title: Dopaminergic modulation of tonic but not phasic GABAA-receptor-mediated current in the ventrobasal thalamus of Wistar and GAERS rats.
abstract: Activation of GABA(A) receptors by GABA causes phasic and tonic conductances in different brain areas. In the ventrobasal (VB) thalamus, tonic inhibition originates from GABA acting on extrasynaptic receptors. Here we show that dopamine (DA), the D2-like agonist quinpirole and the selective D4R agonist PD-168,077 decrease the magnitude of the tonic GABA(A) current while D1-like agonist SKF39383 lacks any significant effects in VB neurons of Wistar rats. On the other hand, DA and D1/D2 receptor activation does not alter phasic GABA(A) conductance. As we previously reported that an increased tonic GABA(A) current in VB neurons is critical for absence seizure generation, we also investigated whether D2-D4 receptor activation is capable of normalizing this aberrant conductance in genetic absence epilepsy rats from Strasbourg (GAERS). Quinpirole and PD-168,077 selectively reduces tonic GABA(A) current as in normal rats. Therefore, it is conceivable that some DA anti-absence effects occur via modulation of tonic GABA(A) current in the VB.
authors.affiliation: Neuroscience Division, School of Biosciences, Cardiff University, Cardiff, UK.
authors.forename: Josue G
authors.initials: JG
authors.lastname: Yagüe
authors.forename: Anna
authors.initials: A
authors.lastname: Cavaccini
authors.forename: Adam C
authors.initials: AC
authors.lastname: Errington
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Crunelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Giovanni
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004832:Epilepsy, Absence / Q000235:genetics / Q000473:pathology*; D018682:GABA Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000378:metabolism*; D013788:Thalamus / Q000166:cytology* / Q000378:metabolism
chemical_list: D015259:Dopamine Agents; D018682:GABA Agents; D018080:Receptors, GABA-B; D004298:Dopamine
keywords: Absence epilepsy; Dopamine; GABA(A) receptors; Patch-clamp; Tonic inhibition; Ventrobasal thalamus