Short CommunicationDopaminergic modulation of tonic but not phasic GABAA-receptor-mediated current in the ventrobasal thalamus of Wistar and GAERS rats

- Dopamine and D2-D4R activation decrease tonic exstrasynaptic GABAA-mediated current of the ventrobasal thalamus neurons.
- Dopamine and D2-D4R activation does not alter phasic synaptic GABAA-mediated current.
- D1Rs do not modulate either phasic or tonic GABAA-mediated current in the ventrobasal thalamus.
- D2-D4R activation normalises aberrant eGABAA-mediated current of the ventrobasal thalamus of GAERS.

Activation of GABAA 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 GABAA 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 GABAA conductance. As we previously reported that an increased tonic GABAA 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 GABAA current as in normal rats. Therefore, it is conceivable that some DA anti-absence effects occur via modulation of tonic GABAA current in the VB.