Vol 4 n° 4 - Drug Development
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leep-wake alternation is an essential component of human biological rhythms, and physiological processes accompanying sleep are fundamental to body recovery.As reflected in waking performance, sleep is one of the major determinants of brain function. Quality of life, productiv- ity, health, and effective education all depend on the qual- ity of normal brain function. However, the economic and social development in our modern society has led, and will lead, to chronic disruption of sleep in a sizeable proportion of the population.The main contributors to these disrup- tions can be classified as either environmental (noise and light pollution), economic/societal (shift-work schedule), or pathological (sleep disorders).The detrimental effects of  these  factors  on  sleep  increase  with  age  and  are expected to have an even larger impact in the future, given the aging population and the increased prevalence/inci- dence of shift work. Sleep-wake mechanisms and drug discovery: sleep EEG as a tool for the development of CNS-acting drugs Luc Staner, MD Keywords:  rapid  eye  movement  sleep;  EEG;  slow  wave  sleep;  acetylcholine; depression
Author  affiliations:  FORENAP,  Institute  for  Research  in  Neuroscience  and Neuropsychiatry, Rouffach, France
 Address  for  correspondence:  Dr  Luc  Staner,  Sleep  Laboratory,  FORENAP, Institute  for  Research  in  Neuroscience  and  Neuropsychiatry,  BP29,  68250 Rouffach, France (e-mail: luc.staner@forenap.asso.fr) S Sleep laboratory investigations constitute a unique noninvasive tool to analyze brain functioning. Polysomnographic recordings, even in the very early phase of development in humans, are mandatory in a developmental plan of a new sleep-acting compound. Sleep is also an interesting tool for the development of other drugs acting on the central ner- vous system (CNS). Indeed, changes in sleep electroencephalographic (EEG) characteristics are a very sensitive indication of the objective central effects of psychoactive drugs, and these changes are specific to the way the drug acts on the brain neurotransmitter systems. Moreover, new compounds can be compared with reference drugs in terms of the sleep EEG profile they induce. For instance, cognitive enhancers involving cholinergic mechanism have been consistently demon- strated to increase rapid eye movement (REM) sleep pressure, and studying drug-induced slow wave sleep (SWS) alter- ation is a particularly useful tool for the development of CNS compounds acting at the 5-HT2A/C  receptor, such as most atypical antipsychotics and some antidepressant drugs. The sleep EEG profile of antidepressants, and particularly their effects on REM sleep, are specific to their ability to enhance noradrenergic or serotonergic transmission. It is suggested that the effects of noradrenergic versus serotonergic reuptake inhibition could be disentangled using specific monoamine depletion tests and by studying drug effects on sleep microstructure. Dialogues Clin Neurosci. 2002;4:342-350. C l i n i c a l   r e s e a r c h 3 4 2