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Curr Opin Neurobiol. 2013 Oct;23(5):831-40. doi: 10.1016/j.conb.2013.04.010. Epub 2013 May 23.

Sites of action of sleep and wake drugs: insights from model organisms.

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Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK. Electronic address:


Small molecules have been used since antiquity to regulate our sleep. Despite the explosion of diverse drugs to treat problems of too much or too little sleep, the detailed mechanisms of action and especially the neuronal targets by which these compounds alter human behavioural states are not well understood. Research efforts in model systems such as mouse, zebrafish and fruit fly are combining conditional genetics and optogenetics with pharmacology to map the effects of sleep-promoting drugs onto neural circuits. Recent studies raise the possibility that many small molecules alter sleep and wake via specific sets of critical neurons rather than through the global modulation of multiple brain targets. These findings also uncover novel brain areas as sleep/wake regulators and indicate that the development of circuit-selective drugs might alleviate sleep disorders with fewer side effects.

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