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LEARNED HELPLESSNESS AND SLEEP: DISCUSSION OF CONTRADICTIONS

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.

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