GABAergic drugs can enhance or attenuate chlordiazepoxide-induced sleep time in a heterogeneous strain of mice

Evidence supports the notion that differences between the Long-Sleep and Short-Sleep selectively-bred lines of mice are attributable to differences in brain excitability and that these differences are mediated by activity of the GABAergic system. The general applicability of this hypothesis to other populations of mice was tested by using an outbred strain of mice. Specifically, a heterogeneous strain of mice was administered several doses of the hypnotic chlordiazepoxide. Additionally, the indirect GABA agonist AOAA, and the GABA antagonists bicuculline, picrotoxin and pentylenetetrazol were administered to independent groups in conjunction with chlordiazepoxide. The results clearly demonstrate that chlordiazepoxide dose-dependently increased hypnosis, while AOAA enhanced, and the antagonists attenuated sleep time. These findings can be used to support the contention that GABA mediates the bidirectional response of Long-Sleep and Short-Sleep mice to CNS hypnotic-depressants; and, further, show that GABA mediation of sleep time in mice is a general phenomenon.