Uridine modulates neuronal activity and inhibits spike-wave discharges of absence epileptic Long Evans and Wistar Albino Glaxo/Rijswijk rats

Abstract

Pharmacological and functional data suggest the existence of uridine (Urd) receptors in the central nervous system (CNS). In the present study, simultaneous extracellular single unit recording and microiontophoretic injection of the pyrimidine nucleoside Urd was used to provide evidence for the presence of Urd-sensitive neurons in the thalamus and the cerebral cortex of Long Evans rats. Twenty-two neurons in the thalamus (24% of recorded neurons) and 17 neurons in the cortex (55%) responded to the direct iontophoresis of Urd. The majority of Urd-sensitive neurons in the thalamus and cortex (82% and 59%, respectively) increased their firing rate in response to Urd. In contrary, adenosine (Ado) and uridine 5'-triphosphate (UTP) decreased the firing rate of all responding neurons in the thalamus, and the majority of responding neurons in the cortex (83% and 87%, respectively). Functional relevance of Urd-sensitive neurons was investigated in spontaneously epileptic freely moving Long Evans and Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. Intraperitoneal (i.p.) injection of 500mg/kg Urd decreased epileptic activity (210-270min after injection) in both rat strains. Intraperitoneal administration of 1000mg/kg Urd decreased the number of spike-wave discharges (SWDs) between 150-270min and 90-270min in Long Evans and WAG/Rij rats, respectively. The effect of Urd was long-lasting in both rat strains as the higher dose significantly decreased the number of SWDs even 24h after Urd injection. The present results suggest that Urd-sensitive neurons in the thalamus and the cerebral cortex may play a role in the antiepileptic action of Urd possibly via modulation of thalamocortical neuronal circuits.

Keywords: 3-AP; 3-aminopyridine; ANOVA; ATP; Absence epileptic rats; Ado; CNS; EEG; Extracellular neuronal activity; FFT; Fast Fourier Transform; GABA; Multibarrel microiontophoresis; N-methyl-d-aspartate; NMDA; Pyrimidine nucleoside; S.E.M.; SWD; Spike-wave discharges; UDP; UTP; Urd; WAG/Rij; Wistar Albino Glaxo/Rijswijk; adenosine; adenosine 5′-triphosphate; analysis of variance; central nervous system; d.w.; distilled water; electroencephalogram; gamma-aminobutyric acid; i.p.; intraperitoneal; spike-wave discharge; standard error of the mean; uridine; uridine 5′-diphosphate; uridine 5′-triphosphate.