POSTNATAL REM SLEEP DEPRIVATION AND DEPRESSION NEW

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					Actas de Fisiología 7, 2001                                                          141

          POSTNATAL REM SLEEP DEPRIVATION AND DEPRESSION:
                   NEW FINDINGS AND HYPOTHESIS

                                  Pingfu Feng
 Sleep Lab., Department of Psychiatry and Behavioral Sciences, Emory University,
                                  Atlanta, USA


It is well documented that postnatal (PN) treatment with clomipramine (CLI) and sev-
eral other drugs, mostly antidepressant and REM sleep (RS) suppressant, produces a
set of behavioral changes exhibited in human depressive disorders. These behavioral
changes include decreased sexual activity, decreased aggression, increased locomo-
tion, decreased pleasure-seeking behaviors, extended immobility in forced swim test,
increased adult alcohol consumption. These drugs have different aminergic effects.
Regardless of their aminergic effects, all tested antidepressant drugs that produce adult
depressive behavior have RS deprivation (RSD) effects. These findings suggested the
hypothesis that PN RSD by the drugs, rather than their different aminergic effects,
mediates the adult depression. Consistent with this hypothesis, Iprindole, an antide-
pressant drug that does not decrease RS, does not produce adult depressive symptoms
after administration to PN rats. RSD by drugs is always confounded by the other, un-
avoidable effects of the drugs. To circumvent such complications, our lab developed a
method for continuous (24 hr/day), long term (weeks) polysomnographic (PSG) re-
cordings and instrumental RSD (IRSD) of PN rats. In our new method, an IRSD and a
yoked control (YC) PN rat shared the same cage but were separated by a vertical wall.
The cage was attached to the platform of a laboratory shaker. The shaker was turned on
when IRSD rats began RS. YC rats were permitted to have RS, while IRSD rats were
not. Our study demonstrated that IRSD of PN rats produces adult behavioral changes
similar to those elicited by PN treatment with CLI. Compared with YC rats, adult IRSD
rats demonstrated diminished sexual behavior, decreased aggressive behavior, increased
RS percentage, and decreased body weight. This result further supports the hypothesis
that PN RSD produces adult depressive behavior.
     PN RS plays a critical role in development has been postulated based on the well-
accepted behavioral phenomena in the early-age: a very high percentage of RS and
during which very frequent phasic muscle twitches occur. Three of our recent studies
using our new method demonstrated the similar result, i.e. PN (no elder than 21 days)
RSD either by drug or by instrumental method produces large portion (45-69% de-
pending on age) of RS reduction without proportional increase of wake. The RS reduc-
tion is largely compensated by NS during PN RSD. This is possibly the answer to the
paradox of why adult RSD alleviates depressive symptoms and PN RSD produces
depression like behaviors. RS reduction without an increase in wakefulness results in a
net loss of stimulation through the reduction of endogenous (self) stimulation generat-
ed during RS without the increase of exogenous stimulation by behavioral movement
during waking periods.
142                                                              Actas de Fisiología 7, 2001

         FUNCTIONS OF SLEEP: SIMPLICITY VERSUS COMPLEXITY

 R.V. Rial1, M.C. Nicolau1,A. Gamundi1, M. Akaarir1, and S.R. Pandi-Perumal2
1Laboratoiri de Fisiologia, Departamento de Biologia Fonamental I Ciencies de la
     Salut, Universitat de les Illes Balears, 07071 Palma de Mallorca, Spain.
 2Department of Physiology, UCLA School of Medicine, Los Angeles, CA 90095,
                                         USA

An important challenge facing sleep researchers is the fact that sleep, although consid-
ered a simple behavior in animals, is rather complex, with many components and mul-
tiple functional and anatomical controlling substrates. As additional factors of this com-
plexity, different animals show sleep with different components, with different depths,
and with different neural controls.
     As a behavior, sleep has been broadly defined by 1) motor rest, 2) elevated sensory
thresholds, 3) easy reversibility, 4) species specific sleeping posture, 5) resting/sleep-
ing locations, 6) circadian organization, and 7) physiological regulation.
     The above sum of characteristics however is heterogeneous, because reversibility,
rhythmicity, and regulation are factors which pervade other ones, acting as regulators
for the amount, intensity, organization, and of the spatial-temporal distribution of sleep.
Regulation exists for the amount of motor activity, sensory processing efficiency, sleeping
posture, and for search of the sleeping site. The existence of multiple regulatory mech-
anisms upon every sleep component could be used as an indicator to the cause of sleep,
i.e., one could state that animals sleep either to be immobile, to achieve sensory rest, or
to maintain a regular contact with the sleeping site as a part of its individual territory.
     However, there is an ascending inclusiveness of sleep characteristics, from simple
to complex organisms: protozoa, (even plants) will regulate their motor rest/activity
cycles, while mammals control the whole set. This inclusiveness could be important
because it also offers cues on the function of sleep: simple species must sleep only to
divide the biological time in accordance with their ability to cope with changes in the
environment. Then additional functions can be added as animals become more and
more complex. However, one should not blindly assign functions to every anatomic or
functional detail found in a living being. Such details could be either mere evolutionary
accidents, or unavoidable byproducts of other truly adaptive characteristics, which, in
principle, could bear no relation to sleep. The problem could be thus to distinguish
between essential characteristics and byproducts.
Actas de Fisiología 7, 2001                                                          143

PARADOXICAL SLEEP DEPRIVATION AND THE ACTIVITY OF THE HPA AXIS

                 Deborah Suchecki, Paula A Tyba and Tatiana M Baía
                          University of Sao Paulo, Brazil
                                    [FOCUS GROUP]



Instrumental methods to induce paradoxical sleep (PS) deprivation also result in an
immediate activation of the hypothalamic-pituitary-adrenal (HPA) axis, suggesting these
methods are stressful. For several years our group has been trying to develop a method
of PS deprivation that would contain the least intervening variables as possible, such as
social isolation and restriction of movements. Recently, a series of papers showed that
animals raised and PS deprived as a socially-stable group in a large water tank contain-
ing 14-15 narrow platforms exhibit attenuated stress indexes, compared to animals
deprived by the same method, but as a socially-unstable group. This method has been
named modified multiple platform method (MMPM) and includes an environmental
control group, where animals are placed on a grid inside the water tank. It is known
that prolonged enhancement of corticosterone (CORT) levels may hinder further ele-
vations of CORT, due to the influence of negative feedback system. Moreover, we
were curious to examine whether animals PS deprived individually (single platform
method [SPM]) or as a group (MMPM) would respond differently to stress. To exam-
ine whether PS deprivation could alter the dynamics of the HPA axis, we submitted
animals PS deprived by the SPM or by the MMPM to a mild stressor (saline injection
+ novelty) or to a more dramatic stressor (5 min session on the elevated plus maze
[EPM]). Appropriate control groups (dry SPM control [SPMC] and the grid control
[GR]), in addition to a cage control (CC) group, were used. Animals were either sacri-
ficed immediately after the deprivation period or at the corresponding time-point for
control groups (time-point 0) or 5, 20 or 60 min after the stressor. In response to the
mild stress, control groups, except GR showed a peak CORT levels at 5 min, which
persisted until the 20-min time-point, returning to basal levels by 60 min. PS deprived
animals, curiously, exhibited a peak of similar magnitude at 5 min, but precipitously
returned to basal levels by 20 min remaining so low by 60 min. In response to the
EPM, control groups exhibited elevated CORT plasma levels at 5 min, which were
further enhanced by 20 min. Except for the GR animals, CORT levels began to lower
but did not return to basal by 60 min. Again PS deprived animals exhibited increased
CORT levels in response to stress without showing the abrupt return to basal levels by
20 min, but doing so by 60 min. Interestingly, MMPM animals exhibited a less anxious
behavior in the EPM, with more entrances and longer time spent in the open arms.
These data indicate that PS deprivation does not hinder the ability of HPA axis to
mount an adequate stress response nor impairs the negative feedback system. Howev-
er, the behavioral response to the EPM appears to be dependent on whether animals are
deprived individually or as a group.

This work was supported by grants from AFIP and FAPESP (CEPID project).