Escapable Shock Research Articles

Hematopoietic Changes in Rats after Inescapable and Escapable Shocks

Bone marrow cell responsiveness to hematopoietic growth factors was investigated in rats only confined or experiencing inescapable, escapable shocks or no electric shock. The results demonstrated a significant reduction in the number of granulocyte-macrophage precursors in the bone marrow of confined rats and of rats exposed to inescapable shocks. The reversibility of this mielossupressive response was seen in both groups and occurred first in the confined animals. No changes were observed in the group submitted to escapable shocks when compared to controls.

Inescapable shock-induced potentiation of morphine analgesia.

Exposure to various stressors potentiates nociceptive and nonnociceptive responses to morphine. These phenomena have received little study despite their seeming generality and importance for understanding analgesia and opiate action. The present experiments characterize inescapable shock (IS)-induced potentiation of morphine analgesia. Rats were exposed to IS, equal escapable shocks (ESs), or restraint (control). Potentiation of analgesia (tail-flick [TF] test and hotplate test) was observed only in rats given IS 24 or 48 hr earlier, in agreement with previously reported learned-helplessness effects. Finally, no change in tail temperature or motor function was found that could be inaccurately interpreted as analgesia. The relevance of these findings to stressor-induced enhancement of morphine analgesia and potential substrates of IS effects are discussed.

Activity Wheel Running Reduces Escape Latency and Alters Brain Monoamine Levels After Footshock

We examined the effects of chronic activity wheel running on brain monoamines and latency to escape foot shock after prior exposure to uncontrollable, inescapable foot shock. Individually housed young (∼50 day) female Sprague-Dawley rats were randomly assigned to standard cages (sedentary) or cages with activity wheels. After 9–12 weeks, animals were matched in pairs on body mass. Activity wheel animals were also matched on running distance. An animal from each matched pair was randomly assigned to controllable or uncontrollable inescapable foot shock followed the next day by a foot shock escape test in a shuttle box. Brain concentrations of norepinephrine (NE), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), 5-hydroxytryptamine (5-HT), and 5-hydroxyindole acetic acid (5-HIAA) were assayed in the locus coeruleus (LC), dorsal raphe (DR), central amygdala (AC), hippocampus (CA1), arcuate nucleus, paraventricular nucleus (PVN), and midbrain central gray. After prior exposure to uncontrollable foot shock, escape latency was reduced by 34% for wheel runners compared with sedentary controls. The shortened escape latency for wheel runners was associated with 61% higher NE concentrations in LC and 44% higher NE concentrations in DR compared with sedentary controls. Sedentary controls, compared with wheel runners, had 31% higher 5-HIAA concentrations in CA1 and 30% higher 5-HIAA concentrations in AC after uncontrollable foot shock and had 28% higher 5-HT and 33% higher 5-HIAA concentrations in AC averaged across both foot shock conditions. There were no group differences in monoamines in the central gray or in plasma prolactin or ACTH concentrations, despite 52% higher DA concentrations in the arcuate nucleus after uncontrollable foot shock and 50% higher DOPAC/DA and 17% higher 5-HIAA/5-HT concentrations in the PVN averaged across both foot shock conditions for sedentary compared with activity wheel animals. The present results extend understanding of the escape-deficit by indicating an attenuating role for circadian physical activity. The altered monoamine levels suggest brain regions for more direct probes of neural activity after wheel running and foot shock.

Escapable stress modulates retention of spatial learning in rats: Preliminary evidence for involvement of neurosteroids

The ability to escape stress has been shown to protect an organism from many of the deleterious effects of stress exposure. It has been suggested that this amelioration could be mediated by the release of an endogenous benzodiazepine-like substance in the brain demonstrated 2 h poststress. Since benzodiazepines possess amnestic as well as antianxiety actions, the possibility of memory alterations in coping subjects was evaluated. Animals were randomly assigned to three groups: escapable shock, yoked inescapable shock, and no shock. Immediately poststress, all subjects were trained in a circular water maze. Acquisition and retention data were obtained in a between-subjects design at three different retention intervals (2 h, 4 h, and 24 h postshock). Results revealed no significant group differences in acquisition of the spatial learning task between groups. However, subjects in the escapable stress group had enhanced retention at 2 h postshock but were significantly impaired 24 h postshock relative to yoked-inescapable-shock and nonshock controls. Blockade of the synthesis of neuroactive GABAA positive steroids by 4-MA, a 5-alpha reductase enzyme inhibitor, blocked this effect. Thus, neuroactive steroid metabolites may play a critical role in the escapable-stress-induced retention deficit seen at 24 h poststress. These observations suggest that altered memory in the escapable-shock subjects may impart stress resiliency by reducing proactive interference of prior stress on subsequent learning and physiology.

Stress controllability influences the ataxic properties of both ethanol and midazolam in the rat.

Rats were administered either 80 escapable shocks or yoked inescapable shocks, were then injected with saline or several ataxic doses of either ethanol or midazolam, and then had their motoric impairment assessed by Rotarod performance. No motoric impairment was observed following saline injection. However, inescapable shock impaired Rotarod performance in response to both ethanol and midazolam at 2 hr, but not immediately poststress. Conversely, escapable shock reduced the ataxic potency of ethanol, although it had no influence on midazolam-induced ataxia. These results indicate functional alterations in behavioral reactivity to low doses of several classes of central nervous system depressants by psychological dynamics of stress exposure. Our findings demonstrate the impact of stress controllability on behavioral reactivity to two classes of drugs of abuse.

Cold-induced amnesia blocks escape deficits in the cockroach (Periplaneta americana).

For three consecutive days, four groups of adult cockroaches (Periplaneta americana) were yoked to cockroaches receiving escapable shock. The four groups of subjects received either inescapable shock followed by exposure to 12 minutes of cold (2 degrees C), inescapable shock followed by no exposure to cold, no-shock followed by exposure to cold, or no-shock followed by no exposure to cold. 24 hr. later all five groups were run on a different escape task. The cockroaches exposed to inescapable shock followed by no exposure to cold showed the usual escape deficit. The cockroaches exposed to inescapable shock followed by exposure to cold did not alter from the escapable shock cockroaches or the controls.

Stress and consumption: inescapable shock, neophobia, and quinine finickiness in rats.

Exposure to inescapable shock has been shown to result in reduced consumption of quinine in water (the finickiness effect) in rats. In the present experiment, (a) a clear difference in finickiness occurred between male adult rats exposed to inescapable shock and those exposed to escapable shock (the first such demonstration), (b) finickiness was reinstated 20 days later, and (c) finickiness was eliminated by quinine exposure prior to treatment. The first 2 results support the role of uncontrollability and/or unpredictability in finickiness and extend its potential impact to long-term consequences. This allows greater potential for the modeling of long-term effects, such as eating disorders and depression in humans. The finding that preexposure to quinine eliminated finickiness is contrary to current accounts of the effect. Accounts of finickiness are proposed in terms of classically conditioned aversions, bitterness, and neuropeptide control of ingestion.

Strain-dependent escape deficit in two rat models of learned helplessness

The shuttle box escape deficit produced by prior inescapable shock (IS) or by escapable shock (ES) was investigated in Koltushi high- (KHA) and low-avoidance (KLA) rat strains, genetically selected on the basis of divergent acquisition of a conditioned avoidance response in a two-way shuttle box. IS enhanced escape failures only in KHA rats. In contrast, ES produce escape deficit only in KLA rats. These data suggest that the learned helplessness interpretation of escape deficit might be relevant only when IS is administered to KHA rats. In the case of KLA rats exposed to ES, escape deficit represents a coping behavior.

In vitro neurotransmitter release in an animal model of depression

Sprague-Dawley rats exposed to uncontrollable shock can be separated by a subsequent shock escape test into two groups: a “helpless” (LH) group which demonstrates a deficit in escape behavior, and a “nonlearned helpless” (NLH) group which shows no escape deficit and acquires the escape response as readily as naive control rats (NC) do. The present studies were designed to examine the correlations between the behavioral differences and the changes of in vitro neurotransmitter release seen in these three groups of rats. The major finding concerned a significant increase in endogenous and K +-stimulated serotonin (5-HT) release in the hippocampal slices of LH rats. There were no apparent differences in acetylcholine, dopamine and noradrenaline release in the hippocampus of LH rats as compared to NLH and NC rats. These results add further support to previous studies in our laboratory which implicate presynaptic 5-HT mechanisms in the behavioral deficit caused by uncontrollable shock.

Circadian effects of escapable and inescapable shock on the food intake and wheelrunning of rats

The feeding and running activities of rats were used to characterize the stressful effects of footshock. A 12-hour light/dark cycle was continuously in effect. During the preshock stage, all rats lived in individual cages where they could drink water, press a lever once for each 45 mg food pellet or run in an attached running wheel. During the shock stage, rats were moved to cages where they could drink and eat, but not run. Five s of light followed by 5 s of a light + tone compound preceded five progressively more intense shock levels. Rats in group AE were trained to pull a ceiling chain to avoid/escape from footshocks that were scheduled 24 hours per day. In group YS, the frequency, intensity and pattern of shocks for a rat were yoked to a rat in group AE. Rats in group CN were not shocked. During recovery, rats were allowed to resume running. During the dark, but not the light of the first day of shock, the intake of groups AE and YS was less than the intake of group CN. By the third day of shock, the food intake of group AE recovered and was no longer different from the intake of group CN. Intake of group YS remained less than the intakes of groups AE and CN during the remainder of the shock stage. When shock was terminated, the intake of the YS group recovered, but neither running nor food intake differed among groups. These results suggest that although inescapable shock disrupts food intake more than escapable shock, this disruption is specific to the duration of the shock stage and depends on rat's circadian pattern of intake.

Controllability and duration of stress alter central nervous system depressant-induced sleep time in rats.

Rats were exposed to either 80 escapable shocks or yoked inescapable shocks and then injected with several hypnotic doses of sodium pentobarbital, midazolam, or ethanol; their sleep-time duration was compared with that of naive controls. Inescapable shock exposure resulted in a significant increase in ethanol-induced sleep time compared with the escapable shock and naive control groups. Both escape and yoked groups showed an increase in barbiturate-induced sleep time compared with controls, although no difference was observed for midazolam. Acute stress (twenty 5-s inescapable shocks) did not alter the depressant-induced sleep time for any of the drugs tested. These results illustrate the importance of psychological aspects of stress and its influence on the potency of certain depressants.

食物獲得に対する対処可能性の喪失が後のディスク引き逃避学習に及ぼす効果

The present study examined wheter or not a loss of control over food acquisition would interfere with disk pulling shock escape learning. The loss-of-control rats, which had experienced loss of control over food delivery, and the lack-of-control rats, which had received noncontingent food delivery without a prior history of control over food, were impaired on acquisition of the fixed ratio (FR) 2 disk-pull escape compared to the response-contingent, the continous-reinforcement (CRF)-control, and the home-cage-control rats, which did not differ from each other

Information processing in short-term memory and event-related brain potentials

Rats were either given 80 escapable shocks, yoked inescapable shocks, restraint or given no treatment. Two hours later all subjects received i.p. injection of bicuculline (4, 6 or 8 mg/kg) and were immediately tested for latency to initial myoclonic jerk and clonus. The latency to clonic convulsion was dramatically affected by prior shock treatment, and the direction of this change depended upon the escapability/inescapability of the shock. Subjects that were given escapable shock a delay of onset to seizure, while subjects inescapably shocked demonstrated a decreased latency to clonus in comparison to restrained and naive controls. It was also demonstrated that if the subjects were tested immediately following a stress experience, both the 80 escapable and inescapable shock condition protected against bicuculline-induced seizures in comparison to the control condition. Finally Experiment 2 confirmed a previous finding that less stress, i.e., 20 inescapable shocks, protects against seizures when the animals are challenged with bicuculline either immediately or 2 h later. Our suggestion is that control over stress may facilitate GABAergic transmission, and this may be the mechanism whereby coping protects against the behavioral and physiological disruption produced by exposure to a stressor.

Modulation of [3H]Paroxetine Binding to the 5‐Hydroxytryptamine Uptake Site in an Animal Model of Depression

The effects of learned helplessness on the 5-hydroxytryptamine (5-HT) uptake site were studied in rats using [3H]paroxetine binding. This ligand was chosen because it was demonstrated to label directly the 5-HT uptake site whereas the [3H]imipramine binding site has been demonstrated to be heterogeneous in nature. Moreover, [3H]imipramine appears to bind to a presynaptic recognition site different from the uptake site. Exposure to uncontrollable shock training and testing resulted in an overall increase in [3H]paroxetine binding in all the groups studied [nonhelpless (NLH), learned helpless (LH), spontaneously helpless (SPLH)] as compared to naive controls (NC). However, the increase in [3H]paroxetine binding was significantly higher in the LH and SPLH groups. The maximum number of [3H]paroxetine binding sites in the rat hippocampus was increased significantly in learned helpless rats (LH and SPLH) at day 4 and day 30 after the shock escape test as compared to NC and NLH rats. By contrast, in the rat hypothalamus the maximum number of [3H]paroxetine binding sites was reduced significantly in the LH rats as compared to naive controls and NLH rats during the same time course. There was no change in [3H]paroxetine binding sites in any other brain regions examined in LH, NLH, and NC rats. The results suggest that a hippocampal hypothalamic connection might play a role in the serotonergic mediation of learned helpless behavior.

Stimulus control of immunization against chronic learned helplessness

Two experiments investigated the effectiveness of multiple (five) sessions ofsignaled escapable­ shock pretraining in preventing (immunizing against) the shock-escape impairment produced by an equal number of sessions of signaled inescapable shock. In Experiment 1, rats were exposed to 50 pairings per session of a white-noise stimulus with escapable shock during the immuniza­ tion phase. Subsequently, they were exposed to 50 pairings per session of a different (houselight) stimulus with inescapable shock. Shock-escape performance in a shuttlebox test with constant illumination revealed no evidence of immunization relative to the performance ofrats given five prior sessions of light-signaled inescapable shock only. Experiment 2 was identical in a11 respects to Experiment 1, except that both the escapable- and the inescapable-shock phases for animals in the immunization treatment group involved the same stimulus (houselight) as a shock signal. Under these circumstances, the prior escapable-shock training significantly reduced the shuttle­ box escape deficit engendered by chronic exposure to signaled inescapable shock; performance in the shuttlebox was not reliably different from that ofrats exposed to signaled escapable shock alone. These findings suggest that, under chronic conditions, the development of stimulus con­ trol using Pavlovian conditioning procedures may serve to modulate the normally prophylactic influence on later shock-escape acquisition of serial exposure to escapable and inescapable shocks.

Reconsideration of the role of competing responses in demonstrations of the interference effect (learned helplessness).

In Experiment 1a, rats trained to escape shock by performing a 2-s inactive response were less impaired on a subsequent 2-way shuttle response than their yoked counterparts that received inescapable shock. In contrast, in Experiment 1b, rats trained to escape shock by performing a longer duration inactive response were more impaired on the subsequent escape task than their inescapably shocked counterparts. In Experiment 2, the results of Experiments 1a and 1b were replicated, and the inactive responses performed during pretreatment by both the escapable and inescapable shock groups were assessed and correlated with test stage 2-way shuttle escape performance. These activity data indicate that inactivity during pretreatment shock in both escapable and inescapable shock groups was a highly reliable predictor of subsequent 2-way shuttle performance, irrespective of the pretreatment shock contingency to which these Ss were exposed.

Differential effects of escapable and inescapable footshock on hippocampal theta activity.

Three groups of rats were exposed to escapable shock, inescapable shock, or no shock using procedures known to induce learned helplessness effects. Twenty-four hours later, hippocampal electroencephalograms were recorded from freely moving subjects. A 5-s probe shock was delivered after 15 min, and recording continued. Frequency analyses revealed no differences between the pretreatment groups during the first recording segment. Immediately after the probe shock, however, trains of immobility-related theta activity were observed in both the escapable-and no-shock groups. No such activity was observed in the inescapable-shock group. Because immobility followed the probe shock in all groups, this relative impairment was not due to differential motor activity. These results offer in vivo support for in vitro findings suggesting that hippocampal activity is sensitive to event contingencies and is involved in stress-induced learning deficits.

5-HT 1b, receptors in an animal model of depression

After exposure to a 0.8 mA course of uncontrollable shocks, Sprague-Dawley rats can be differentiated into two distinct groups defined in term of their performance in a shock escape paradigm. Learned helpless (LH) rats do not learn to escape a controllable shock while non-helpless (NLH) rats learn this response as quickly as naive controls (NC) rats do. The current experiments were designed to extend our studies of 5-HT receptors in these three groups of rats. The major finding in the present study concerned post-synaptic 5-HI receptor effects in the cortex, hippocampus, septum and hypothalamus of LH rats. These included an up regulation of 5-HT 1b receptors in the cortex, hippocampus and septum in LH rats. In contrast, 5-HT 1b receptors in the hypothalamus of LH rats were down-regulated. These results implicate serotonergic mechanisms in the behavioral deficit caused by uncontrollable shock with a limbic-hypothalamic circuit serving as a center for adaptation to stress.

Immunization against Learned Helplessness in the Cockroach (Periplaneta Americana)

Cockroaches exposed to one day of escapable shock prior to three days of inescapable shock did not become helpless on a shuttlebox-escape task. Like dogs and rats, cockroaches are immunized against learned helplessness by prior experience with escapable shock.

Circadian rhythmicity and behavioral depression: II. Effects of lighting schedules

Two studies explore the relationship between rhythmicity and behavioral depression. Behavioral depression was induced using inescapable footshock, and assessed by measuring subsequent responses to escapable shock, in rats housed under different light-dark conditions. Experiment 1 compared escape performance in free-running and entrained animals following inescapable shock. Free-running and entrained animals did not exhibit differential vulnerability to the effects of inescapable shock. In addition, there were no systematic effects on phase following shock. However, several free-running animals showed increased circadian period following shock, and lengthening of period was significantly correlated with escape performance. Individual differences in baseline period or phase were not predictive of escape performance. In Experiment 2, “aftereffects” of entrainment to long or short light-dark cycles were utilized to create groups of animals with long or short free-running periods. After the administration of inescapable shock, escape performance was tested. There were no significant differences among experimental groups in escape performance. These results suggest that plasticity of circadian period, but not baseline period per se, may be associated with the ability to adapt to environmental challenges.