CommentaryGABA mechanisms and sleep
Section snippets
GABAA binding site
The function of the GABA receptor binding site is to open a chloride channel. Some time ago it was shown that the global central increase of GABA by i.c.v. infusion of GABA or inhibition of GABA transaminase increased slow-wave sleep and induced a 64% drop of paradoxical sleep without rebound effect in cats (Karadzic, 1966, Holmes and Sugden, 1975), and did not influence the recovery of paradoxical sleep after selective deprivation in rats (Juan de Mendoza et al., 1973). In humans it seemed to
GABAB receptors
These receptors are involved in sleep–waking regulation as shown by lethargic (lh/lh) mice which have increased numbers of GABAB receptors in the cortex and thalamus (Lin et al., 1993, Lin et al., 1995). Moreover, GABAB receptor antagonists infused in the thalamus decrease EEG slow waves and deep slow-wave sleep while light slow-wave sleep is increased (Juhasz et al., 1994). These compounds are used to alleviate absence-epilepsy in humans (Marescaux et al., 1992, Bittinger et al., 1993) partly
GABAC receptors
Hitherto, it has been difficult to study the influence of the GABAC receptor on behavior since the agonist trans-4-aminocrotonic acid (TACA) and its cis-enantiomer CACA, the first compounds acting on this receptor to be identified, were not specific, like the first antagonists (Bormann and Feigenspan, 1995, Quian and Dowling, 1996). However, in 1996 the first selective antagonist was uncovered: (1,2,5,6-tetrahydropyridine)-methylphosphonic acid (TPMPA) (Murata et al., 1996, Ragozzino et al.,
Conclusion
The three currently identified GABA receptors have similar hypnotic effects when stimulated. Some differences appear when the quality of sleep is examined. Slow-wave sleep is enhanced in all cases. It can be strongly hypothesized that when antagonists promote waking, agonists, where available, will increase sleep. The intermediate stage is extended at the expense of paradoxical sleep by barbiturates, most benzodiazepines and steroids but not by new-generation hypnotics. GABAB and GABAC receptor
Note added in proof
Kauer et al. (2001) confirmed that the medulla prepositus hypoglossi nucleus regulates paradoxical sleep by GABAergic neurons which inhibit locus coeruleus neurons.
Acknowledgements
I thank Professor G. Morgan for correction of the English.
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