Study of a GABA(c) receptor antagonist on sleep-waking behavior in rats

Rationale: gamma -Aminobutyric acid (GABA) is the main inhibitory transmitt er of the brain. The involvement of GABA(A) and GABA(B) receptors in sleep- waking processes is well established. Objectives: This research studied the influence of GABA(C) receptors. Methods: The rats were randomly infused in the fourth ventricle with vehicle and 25, 50, and 100 mug (1,2,5,6,-tetrah ydropyridine)-methylphosphinic acid (TPMPA), a specific antagonist of GABA, receptors. Results: Principally at 50 mug, the molecule induced an increas e of waking from 44.7% to 61.7% (P<0.003), which was the consequence of enh ancement of both active and quiet wakefulness. Total slow wave sleep was de creased, particularly the slow-wave stage from 39% to 27.7% (P<0.02). Parad oxical sleep was also decreased from 14.5% to 9.1% (P<0.01). Conclusions: G ABA(C) receptors are also involved in sleep-waking regulation. Since the se nsitivity of GABA(C) receptors to GABA is much higher than that of GABA(A) and GABA(B) receptors, GABA(C) receptor modulators could be potential medic ations acting at low doses with fewer side effects.