Sleep GABA

Acetylcholine, noradrenaline and serotonin all play a role in inducing sleep. GABA, dopamine and some neuropeptides influence sleep-inducing activity in cholinergic neurons. 

Fused isoxazoles (631) were prepared as GABA analogs (75MI41604) and some exhibited CNS depression effects (74JAP(K)7480062) or were effective as minor tranquilizers, muscle relaxants and/or sleep inducers (76USP3966748, 79USP4163057). 

Sleep and its modulation by N- and N,0-heterocyclic drugs that affect y-aminobutyric acid (GABA) receptor function 99AG(E)2852. 

Molecnlar Mechanisms Underlying Sleep Focns on GABA... 

Setting aside the general anaesthetics, which do not directly modify the function of any particular neurotransmitter, all the drugs that are used to induce sleep, i.e. the hypnotics , augment the function of GABA and so directly depress neuronal function and probably facilitate cortico-thalamic synchrony. Most of them are benzodiazepines... 

Most hypnotic drugs act on GABA receptors. It is reasonable to hypothesize that hypnotic actions are mediated by the GABA receptors on wake-promoting neurons innervated by POA sleep-active neurons, but there is little study of this problem. However, there is evidence that GABAergic anesthetics induce c-Fos IR in the VLPO and suppress c-Fos IR in histaminergic neurons (Nelson et al, 2002). 

Nitz, D. Siegel, J. M. (1996). GABA release in posterior hypothalamus across sleep-wake cycle. Am. J. Physiol. 271, R1707-12. 

Gervasoni, D Darracq, L., Fort, P. et al. (1998). Electrophysiological evidence that noradrenergic neurons of the rat locus coeruleus are tonically inhibited by GABA during sleep. Eur. J. Neurosci. 10, 964-70. 

Lee, R. S., Steffensen, S. C. Henriksen, S. J. (2001). Discharge profiles of ventral tegmental area GABA neurons during movement, anesthesia, and the sleep-wake cycle. J. Neurosci. 21, 1757-66. 

Figure 3.1 Schematic representation of communication between pontine cholinergic REM-ON, NA-ergic REM-OFF and GABA-ergic neurons in the brainstem and influence of brainstem wake- and sleep-inducing areas on REM-ON and REM-OFF neurons for the regulation of REM sleep. Refer to the text for details. The abbreviations are same as in the text (+) indicates excitation and (—) indicates inhibition.

GABA(B) receptor antagonist on the sleep-waking cycle in the rat. Brain Res. 773, 8-14. 

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