VADIM S. ROTENBERG vadir@post.tau.ac.il
Homeostasis, 37 1996, No 1-2
Learned helplessness (LH) is considered to be an experimental
model of depression and/or anxiety (Seligman, 1975, Maier, 1984, Van
der Kolk, 1985, Petty et al, 1994).Sleep structure is a sensitive
marker of human affective disorder in depression (Kupfer, 1976, 1978)
as well as in anxiety (see Rotenberg, Boucsein, 1993): REM latency is
decreased and first REM period is often increased. A genetic animal
model of depression - Flinders Sensitive Line rats - demonstrate an
exaggerated immobility when exposed to mild stressors, and this
immobility is accompanied by an increased REM sleep amount and reduced
REM sleep latency (Overstreet et al, 1994).
The first fundamental study of sleep in LH was performed only
recently (Adrien et al, 1991 a, b). Avoidance training was initiated 48
hours after the initial inescapable shock preconditioning. Rats were
placed individually in shuttle-boxes and subjected to 30 avoidance
trials with 3 sec light signals. If no response occurred during these 3
seconds, shock was presented for maximum 3 sec. Avoidance sessions were
performed on days 2, 4, 8 and 11 morning, between 10 and 11, and the
sleep - wakefulness parameters were collected during the 15 day
recording period. After initial inescapable shocks all rats were
divided into 3 groups one which was submitted to paradoxical sleep (PS)
deprivation using the platform technique, one which stood on a large
platform, and one which was not submitted to the platform protocol. The
two former groups were placed on their respective platforms from 17 00
until 10 00 the next morning. From 11 00 until 17 00 after training
sessions rats were housed in their home cages and allowed to sleep
freely.
This study seems to confirm the similarity between LH and
depression: PS requirement was slightly increased after LH training,
while PS deprivation (PSD) induced a reversal in the escape failures -
in helpless rats the index of helplessness was significantly lower in
the PS deprived group than in both control groups. Consequently, the
outcome of PSD in LH seems to be in the same direction as the outcome
of PSD in depression (Vogel, 1975): LH became less prominent.
In a recent study Maudhuit & Adrien (1994) have shown that
in rats repeated short lasting PS deprivation had the same behavioral
effect as the subchromc treatment with antidepressants in the LH
paradigm. PS deprivation altered also the response of raphe dorsahs
neurons to 5HT reuptake blocker in the same way as a chronic treatment
with antidepressants.
However, the relationship between LH and PS seems not to be so
simple and it is worth-while to analyze data of this investigation in
detail.
In Adrien's study, inescapable shocks have been presented
as a pretraining procedure for 1 hour. Whether such procedure by itself
caused LH or not, remains unknown, because after this procedure animals
were not tested. It is possible to hypothesize that LH was not induced.
The sleep structure after inescapable shocks was significantly
different from the sleep structure after LH induction. PS latency was
increased and PS was reduced. Adrien's explanation that these
alterations of the sleep structure were caused by an acute stress is
plausible because the control groups demonstrated similar alteration
after their first exposures to shocks, though escapable.
According to the Search Activity concept (Rotenberg &
Arshavsky, 1979, Rotenberg, 1984, 1993, 1994), acute and short lasting
stress is usually accompanied by search activity and reduced PS
requirement. Search activity is defined as an activity which may change
the situation (or at least the subject's attitude to it) in absence of
a precise prediction of the outcome. Search activity can be regarded as
a psychobiological state which covers self-stimulation in animals,
creative behavior in humans, as well as exploratory and active defense
behavior (Fight/Flight) in both species. The opposite state,
renunciation of search, is manifested in neurotic anxiety and
depression in humans, in freezing in animals, and also in LH, panicky
behavior and stereotyped behavior in both species. It was shown
(Rotenberg & Arshavsky, 1979a, Rotenberg, 1984) that all forms of
behavior which included search activity increased body resistance to
various forms of artificial and natural pathology, while renunciation
of search decreased body resistance and accelerated the development of
artificial pathology. According to the Search Activity concept, the
function of PS is to compensate the deficit of search activity, if such
deficit had accumulated in the previous wakefulness and to restore
search activity for the subsequent wakefulness. As a result, search
activity is expected to decrease and renunciation of search to increase
the REM sleep requirement (see for details Rotenberg, 1984, 1993).
The experimental group of Adrien's animals which had received
the initial experience of inescapable shocks, displayed LH upon
exposure to the first session of escapable shocks, while the amount of
PS was positively correlated to the index of helplessness. According to
these data it is possible to suggest that the exposure to inescapable
shocks was too short to produce LH by itself, but caused acute stress.
However, search activity which was displayed by the animal in this
state of acute stress does not help it to avoid the punishment and
that's why the animal was predisposed to the development of LH in a
similar situation. When the animal was exposed once more to the shocks,
though escapable, the previous experience of the inescapable shocks
caused a disorganization of behavior and blocked the animals' ability
to recognize that these shocks are escapable. This conclusion is in a
good agreement with data that a previous inescapable stress sensitizes
the hippocampus to an increased norepinephrine release in response to a
subsequent smaller stressor /Petty et al, 1994) which is followed by
eventual depletion (Tsuda et al, 1986) and predisposes animals to LH
(Irvin et al, 1986, Martin et al, 1987). At the same time the animal in
Adrien's investigation does not have sufficient information to predict
that the recent shocks would be restricted in time and space. As a
result, these shocks caused a generalized LH, and the PS requirement
was increased . Such an outcome was predicted by the search activity
concept which considers generalized LH as a renunciation of search.
However, it is necessary to explain why the LH related increase
in PS was only transient and disappeared in subsequent sessions,
although the helpless group exhibited significantly more escape
failures than controls during all shuttle box sessions (Adnen et al,
199la). I suggest that the plausible explanation is that the nature of
LH was changed in the course of the shuttle box sessions. The animal
learned that the shocks are limited in time and space. As a result
generalized LH has been replaced by a conditioned LH tied only to
specific conditions. The animal remains active in all other situations
(Abramson et al, 1978). Such restricted LH does not contribute to
renunciation of search as a global state and does not require an
increase in PS. The term "learned helplessness" seems to be appropriate
only for the conditioned LH, while the global LH is rather
"renunciation of search". This approach may be crucial for
understanding different outcomes of chronic stress. It has been shown
(Yehuda et al, 1993) that the activity of the
hypothalamus-pituitary-adrenal axis may drop in conditions of repeated
or chronic stress. In rats, daily administration of stressors (forced
swimming, noise, immobilization, cold) led sometimes to a gradual
attenuation of the stress response. In other cases, the adrenocortical
response persisted and lead to numerous somatic disorders. According to
Yehuda et al, 1993, the severity, controllability and/or predictability
of the chronic stressor may impede habituation.
Chronic stress can cause physiological deterioration and
exhaustion if combined with a generalized helplessness ("renunciation
of search") whereas conditioned helplessness is associated with
attenuated hormonal response. Exactly in this condition a
superimposition of a novel, acute stressor can increase the attenuated
ACTH level (and brain norepinephrine release and synthesis, Valentino,
1994) because search activity is not inhibited.
The second important question is why PS deprivation induced a
reversal of the escape failures in helpless rats (Adrien et al, 1991).
According to the Search Activity concept PSD on a small platform can
cause LH by itself because animal is restricted in its behavior, cannot
perform the search activity, is continuously punished for attempts to
satisfy its natural need in PS, and is thus unable to compensate
renunciation of search in PS. Long lasting PS deprivation causes a
decrease in aggresive and exploratory behaviors and induces passive and
depressive behavior probably due to the exhaustion of brain
catecholammes (see Current Research of Sleep and Dreams, 1966,
Mollenhour et al, 1977). However, a short-lasting PS deprivation
usually causes an opposite reaction: the animal becomes overactive and
overmotivated. Interestingly, the same nonmonotonous relationship
between the duration of the treatment and behavior characterizes the
development of LH after the first exposure to the inescapable shock -
the animal becomes overactive in the open field and PS requirement is,
therefore, not increased - while later LH is formed and behavior
becomes passive (Overmier, Seligman, 1981).
A common mechanism might be suggested: if the exposure to
frustrating conditions (e g PS deprivation on a small platform or
inescapable shock) is short the animal demonstrates a "rebound,, search
activity. In Adrien's study (1991b) the group of animals with the
conditioned LH was exposed to a short-lasting PS deprivation before
training sessions. Such deprivation was not strong enough to cause
generalized LH, and in addition was accompanied by PS rebound during
subsequent sleep. Moreover, the increased drive for search activity
induced by a short lasting restriction of motor and search behavior on
the small platform induced a "rebound"- exaggerated motor behavior in
the subsequent wakefulness (Rotenberg et al, 1986). The stay on the
large platform was not so frustrating and did not induce the "rebound"
hyperactivity.
PS deprivation in animals and in depressive patients should
not, however, be directly compared. In depressive patients, the PSD
suppresses a functionally deficient PS which is not effective in
restoring the search activity (Rotenberg, 1994), PS deprivation has
therefore a positive effect. In animals PSD excludes a functionally
efficient PS, and has therefore a deleterious effect. The subsequent
activation of the behavior takes place only if the deprivation is short
and the brain resources for search behavior are not exhausted. In
depression these resources are already decreased before PS deprivation.
No comments:
Post a Comment