Effect of two GABA-ergic drugs on the cognitive functions of rapid eye movement in sleep-deprived and recovered rats

Rapid eye movement (REM) sleep is closely associated with nervous functions. The present study aimed to evaluate the effects of gabazine and tiagabine on the cognitive functions (CF) of REM sleep-deprived and sleep recovered rats. Rats were divided into REM sleep deprivation, blank control (CC) and environmental groups. The REM sleep deprivation group was further divided into non-operation (nonOP), sham-operated (Sham), gabazine (SR) and tiagabine groups. Each group was evaluated over five time points: Sleep deprived for 1 day (SD 1 day), SD 3 day, SD 5 day, sleep recovery 6 h (RS 6 h) and RS 12 h. A rat model of REM sleep deprivation was established by a modified multi-platform water method, with CF assessed by Morris water maze. Hypothalamic.-aminobutyric acid (GABA) and glutamic acid contents were measured via high performance liquid chromatography. The number and morphology of hypocretin (Hcrt) neurons and Fos in the hypothalamus, and GABA(A)R alpha 1-induced integral optical density were detected by immunofluorescence. Compared to the CC group, the nonOP and Sham group rats CF were significantly diminished, Fos-positive and Fos-Hcrt double positive cells were significantly increased, and GABA content and GABA(A)R alpha 1 expression levels were significantly elevated (P<0.05). The tiagabine and CC groups exhibited similar results at three time points. The CF of rats in the SR group were diminished and the number of Fos-positive and Fos-Hcrt double positive cells were significantly increased (P<0.05) at RS 6 h and RS l2 h. GABA content and GABA(A)R alpha 1 expression levels were significantly increased in the SR group at all time points (P<0.05), whereas only GABA(A)R alpha 1 expression levels were significantly increased in the tiagabine group at SD 5 day (P<0.05). The results of the present study indicated that REM sleep deprivation diminished CF, increased the number of Hcrt neurons, GABA content and GABA(A)R alpha 1 expression. Furthermore, all alterations were positively correlated with deprivation time and corrected by sleep recovery, as demonstrated by single-factor multi-level variance analysis at the various time points in each group. Therefore, the Hcrt nervous system may be an eligible therapeutic target for the treatment of insomnia.