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Psychopharmacology (2004) 176: 115122DOI 10.1007/s00213-004-1873-zORIGINAL INVESTIGATIONRegina H. Silva . Sonia R. Kameda . Rita C. Carvalho .
Andr L. Takatsu-Coleman . Suzy T. Niigaki .
Vanessa C. Ablio . Sergio Tufik . Roberto Frussa-FilhoAnxiogenic effect of sleep deprivation in the elevated plus-maze
test in miceReceived: 29 July 2003 / Accepted: 5 March 2004 / Published online: 25 May 2004
# Springer-Verlag 2004Abstract Rationale: Several clinical studies demonstrate that the absence of periods of sleep is closely
related to occurrence of anxiety symptoms. However, the
basis of these interactions is poorly understood. Studies
performed with animal models of sleep deprivation and
anxiety would be helpful in the understanding of the
mechanisms underlying this relationship, but some animal
studies have not corroborated clinical data, reporting
anxiolytic effects of sleep deprivation. Objectives: The
aim of the present study was to verify the effects of
different protocols of sleep deprivation in mice tested in
the elevated plus-maze and to assess the effect of
chlordiazepoxide and clonidine. Methods: Threemonth-old male mice were sleep-deprived for 24 or 72 h
using the methods of single or multiple platforms in water
tanks. Mice kept in their home cages were used as
controls. Plus-maze behavior was observed immediately
after the deprivation period. Results: Mice that were
sleep-deprived for 72 h spent a lower percent time in the
open arms of the apparatus than control animals. This
sleep deprivation-induced anxiety-like behavior was unaffected by treatment with chlordiazepoxide (5.0 and7.5 mg/kg IP), but reversed by an administration of 5 or
10 g/kg IP clonidine. Conclusion: The results indicate
that under specific methodological conditions sleep deprivation causes an increase in anxiety-like behavior in
mice exposed to the elevated plus-maze.Keywords Sleep deprivation . Anxiety . Animal model .
Chlordiazepoxide . ClonidineIntroductionSleep disturbances are often paired with anxiety, and sleep
problems are diagnostic criteria for anxiety disorders
(American Psychiatry Association 1994). Sleep deprivation was reported to produce anxiety in normal humans
(Wyatt et al. 1971; Peeke et al. 1980; Dinges et al. 1997)
and to aggravate symptoms of anxiety disorders (Roy-
Byrne et al. 1986). Although sleep deprivation has been
proposed as a treatment for some psychiatric disorders,
such as depression (Wyatt et al. 1971; Van den Burg and
Van den Hoofdakker 1975; Svendsen 1976; Gerner et al.
1979)...