EFFECT OF THE GABA UPTAKE INHIBITOR TIAGABINE ON SLEEP AND EEG POWER SPECTRA IN THE RAT

1 The sleep profiles induced by agonists and agonistic modulators of g amma-aminobutyric acid(A) (GABA(A)) receptors differ markedly. With re gard to GABA(A) agonists, the effects may be due to the fact that thes e agents are poor substrates for uptake and are therefore likely to ac tivate GABAA receptors tonically. To investigate this possibility, we assessed the sleep effects of two doses (2 and 10 mg kg(-1)) of the GA BA re-uptake inhibitor tiagabine, administered intraperitoneally at li ght onset in 8 rats. Electroencephalogram (EEG) and electromyogram wer e recorded during the first 8 h after the injection. 2 Compared with v ehicle, tiagabine had minimal effects on the temporal pattern of non-r apid eye movement sleep (non-REMS) and on the total time spent therein . However, tiagabine dose-dependently elevated EEG activity during non -REMs, most prominently in the lower frequencies (1-8 Hz) and least pr onounced in the frequencies between 11 and 16 Hz. During the first 2 h after the injection, 10 mg kg(-1) tiagabine elicited repetitive episo des of hypersynchronous EEG waves during wakefulness and slightly supp ressed REMS. Except for these effects, tiagabine hardly influenced the time spent in and EEG activity during wakefulness and REMS. 3 The eff ects of tiagabine on state-specific EEG activity were qualitatively ve ry similar to those elicited by GABA(A) agonists. These findings suppo rt the hypothesis that the influence of GABA(A) agonists on EEG signal s may be caused by tonic stimulation of GABA(A) receptors.