Effect of the GABA uptake inhibitor tiagabine on sleep and EEG power spectra in the rat

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Abstract
1. The sleep profiles induced by agonists and agonistic modulators of gamma-aminobutyric acidA (GABA[A]) receptors differ markedly. With regard to GABA(A) agonists, the effects may be due to the fact that these agents are poor substrates for uptake and are therefore likely to activate GABA(A) receptors tonically. To investigate this possibility, we assessed the sleep effects of two doses (2 and 10 mg kg[-1]) of the GABA re-uptake inhibitor tiagabine, administered intraperitoneally at light onset in 8 rats. Electroencephalogram (EEG) and electromyogram were recorded during the first 8 h after the injection. 2. Compared with vehicle, tiagabine had minimal effects on the temporal pattern of non-rapid 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 pronounced in the frequencies between 11 and 16 Hz. During the first 2 h after the injection, 10 mg kg(-1) tiagabine elicited repetitive episodes of hypersynchronous EEG waves during wakefulness and slightly suppressed REMS. Except for these effects, tiagabine hardly influenced the time spent in and EEG activity during wakefulness and REMS. 3. The effects of tiagabine on state-specific EEG activity were qualitatively very similar to those elicited by GABA(A) agonists. These findings support the hypothesis that the influence of GABA(A) agonists on EEG signals may be caused by tonic stimulation of GABA(A) receptors.