The role of the amygdala and dorsal raphe nucleus in mediating the behavioral consequences of inescapable shock

It has been argued that exposure to inescapable shock produces later behavioral changes such as poor shuttle box escape learning because it leads to the conditioning of intense fear, which later transfers to the shuttle box test situation and interferes with escape. Both fear, as assessed by freezing, and escape were measured in Sprague-Dawley rats 24 hr after exposure to inescapable shock. Lesions of the basolateral region and central nucleus of the amygdala eliminated the fear that transfers to the shuttle box after inescapable shock, as well as the fear conditioned in the shuttle box by the shuttle box shocks. However, the amygdala lesions did not reduce the escape learning deficit produced by inescapable shock. In contrast, dorsal raphe nucleus lesions did not reduce the fear that transfers to the shuttle box after inescapable shock, but eliminated the enhanced fear conditioning in the shuttle box as well as the escape deficit. The implications of these results for the role of fear and anxiety in mediating inescapable shock effects are discussed.     

Corticosterone is involved in foot shock-induced inactivity in rats

Inescapable shock (IS) exposure induces behavioral inactivity, related to behavioral alterations in subsequent tests (i.e., escape failure, and inactivity during shuttle box task). Metyrapone (150 mg/kg, IP), a corticosterone (CS) synthesis inhibitor, administered 3 h prior to IS reduced inactivity during this aversive experience. Forty-eight hours later, when these rats were submitted to a shuttle box task, a reduction in both escape failure and inactivity was observed. These effects were reversed by CS (20 mg/kg, SC) and dose dependent of the synthetic glucocorticoid dexamethasone, both administered 1 h before IS. When metyrapone was administered 3 h before the shuttle box task to IS-exposed animals, escape failures and inactivity were markedly reduced. This effect was subsequently reversed by CS. The dynamics of changes in serum CS concentrations after both IS and shuttle box task paralleled behavioral changes. Animals injected with metyrapone before IS, which displayed active behavior, showed serum CS levels stable at their basal levels after shock, and their secretion pattern was quite attenuated after the shuttle box task, whereas vehicle-, CS alone-, and metyrapone + CS-injected animals showed higher serum CS concentrations post-IS, which slowly decreased to their corresponding basal levels. CS secretion after the shuttle box task was similar for the three groups: it had the same magnitude as after IS, though the decrease was faster. In all groups, animals displayed passive behavior. These results indicate that glucocorticoids are involved in the onset and expression of passive behaviors induced by uncontrollable stressors. Therefore, it is possible to suggest a functional relationship between CS released by exposure to inescapable stressor and the behavioral strategies adopted by rats under this stressful condition.     

Failure to learn to escape by rats previously exposed to inescapable shock is partly produced by associative interference.

2 experiments demonstrated that the effects of prior exposure to inescapable shock on the subsequent acquisition of an escape response in rats is determined by the nature of the contingency that exists between responding and shock termination during the escape learning task, and not by the amount of effort required to make the response or the amount of shock that the S is forced to receive during each trial. Exp I, using 48 male Simonsen rats, showed that inescapably shocked Ss did not learn to escape shock in a shuttle box if 2 crossings of the shuttle box were required (fixed ratio, FR, -2) to terminate shock, but did learn this FR-2 response if a brief interruption of shock occurs after the 1st crossing of the FR-2. Exp II with 72 Ss showed that inescapably shocked Ss learned a single-crossing escape response as rapidly as did controls, but were severely retarded if a brief delay in shock termination was arranged to follow the response. Results are discussed in terms of the learned helplessness hypothesis, which assumes that prior exposure to inescapable shock results in associative interference. (15 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interaction of Pavlovian conditioning with a zero operant contingency: Chronic exposure to signaled inescapable shock maintains learned helplessness effects.

Four studies, with 372 male Holtzman rats, examined the effect of Pavlovian contingencies and a zero operant contingency (i.e., uncontrollability) on subsequent shock-escape acquisition in the shuttle box using triads consisting of escapable-shock (ES), yoked inescapable-shock (IS), and no-shock (NS) rats. After exposure to 50 signals and shocks per session for 9 sessions, interference with shuttlebox escape acquisition for IS Ss was a monotonically increasing function of the percentage of signal–shock pairings during training (Exp I), with 50% pairings producing little or no impairment. Without regard to signaling, ES Ss performed as well as NS Ss. Exp II demonstrated that training and test conditions led to substantial and equal impairment in IS Ss preexposed for 1 session to 100 or 50% signal–shock pairings or to unsignaled shocks. In Exp III, chronic exposure to 100% signaled ISs resulted in impairment only if the signal (light) was present during the shuttlebox test. The continuous presence of the signal during the test contrasted with its discrete (5-sec) presentation during training and suggested that an antagonistic physiological reaction rather than a specific competing motor response had been conditioned. Exp IV provided evidence for possible conditioned opioid mediation. Findings suggest that chronic exposure to uncontrollable shocks maintains the impairment produced by acute exposure only if the shocks are adequately signaled. (63 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dissociation of interference with the speed and accuracy of escape produced by inescapable shock.

Benzodiazepines and naltrexone administered before inescapable shock block behavioral consequences of the inescapable shock such as poor shuttle box escape, reduced activity in reaction to shock, reduced social interaction, and so on. Anxiogenic β-carboline derivatives such as FR-7142 can produce these effects by themselves. In the present study, neither diazepam nor naltrexone had any effect on the interference with Y-maze choice escape accuracy produced by inescapable shock even though they both eliminated the reduction in Y-maze escape response speed produced by inescapable shock. Analogously, FG-1742 did not lead to a reduction in Y-maze choice escape response accuracy even though it did show escape responding. These data imply that inescapable shock interferes with escape choice learning and escape response speed by different mechanisms, the former not involving fear-anxiety processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evidence of contextual fear after lesions of the hippocampus: a disruption of freezing but not fear-potentiated startle

The roles of the dorsal hippocampus and the central nucleus of the amygdala in the expression of contextual fear were assessed using two measures of conditioned fear: freezing and fear-potentiated startle. A discriminable context conditioning paradigm was developed that demonstrated both conditioned freezing and fear-potentiated startle in a context paired previously with foot shock, relative to a context in which foot shock had never been presented. Post-training lesions of the central nucleus of the amygdala completely blocked both contextual freezing and fear-potentiated startle. Post-training lesions of the dorsal hippocampus attenuated contextual freezing, consistent with previous reports in the literature; however, these same lesions had no effect on fear-potentiated startle, suggesting preserved contextual fear. These results suggest that lesions of the hippocampus disrupt the freezing response but not contextual fear itself.     

Failure to learn to escape in rats previously exposed to inescapable shock depends on nature of escape response.

Results of previous studies show that dogs exposed to inescapable shocks in a Pavlov harness subsequently fail to learn to escape shock in a shuttle box. The present 6 experiments attempted to replicate this finding with male Sprague-Dawley rats (N = 182). In agreement with many previous investigations, Exp I found that Ss exposed to inescapable shock did not fail to learn to escape in a shuttle box. Exp II, III, and IV varied the number, intensity, and temporal interval between inescapable shocks and did not find failure to learn in the shuttle box. An analysis of responding in the shuttle box revealed that Ss shuttled rapidly from the very 1st trial, whereas dogs acquire shuttling more gradually. Exp V and VI revealed that Ss exposed to inescapable shock failed to learn to escape when the escape response was one that was acquired more gradually. Exp V utilized a double crossing of the shuttle box as the escape response and Exp VI utilized a wheel-turn response. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Daily fluoxetine administration impairs avoidance learning in the rat without altering sensory thresholds

1. Male rats given daily intraperitoneal injections of fluoxetine (10 mg/kg) were slower to escape foot shock by jumping a low barrier. 2. When switched to a shuttle task requiring two crosses to terminate shock, the FLU-treated animals failed to learn in 55 trials. 3. A second experiment found FLU-treated animals could learn a one-way avoidance response, but were significantly slower to learn than control animals. 4. FLU-treated animals were no different than controls on tests of sensory thresholds for foot shock or heat. 5. Tests of motor behaviors revealed no differences in latency to traverse a narrow beam to reach a goal box, however FLU-treated animals were less active in an open field. 6. Several hypotheses can account for these data, the most promising being that a central motivational system (fear) is less active in FLU-treated animals.     

Regional changes in dopamine and serotonin activation with various intensity of physical and psychological stress in the rat brain

The present study examined whether regional patterns of brain dopamine (DA) and serotonin (5-HT) activation after physical and psychological stress depend on the intensity of that stress. Monoamine concentrations (DA, 5-HT, and their metabolites) were measured using high-performance liquid chromatography with electrochemical detection in eight brain regions of rats exposed to two different intensities of foot shock stress for 30 min (1.5 mA or 2.5 mA) or conditioned fear stress (CFS, after single or repeated foot shock). A low level of foot shock selectively increased the DA metabolism in the medial prefrontal cortex (mPFC), whereas a high level of foot shock increased it in most of the brain regions examined in the present study. A low level of foot shock did not increase the 5-HT metabolism in any regions, but a high-intensity shock increased the 5-HT metabolism in the mPFC, nucleus accumbens, and lateral hypothalamus. Rats that received high-intensity shock displayed more freezing than those that received low-intensity shock in a conditioned fear paradigm (24 h after receiving foot shock, the animals were placed in a shock chamber without being given shock), indicating an augmentation of conditioned fear. The increased DA and 5-HT metabolism were especially marked in the mPFC after CFS following a single foot shock session (2.5 mA). Rats that were repeatedly exposed to 2.5 mA foot shock for a period of 10 days displayed a greater degree of freezing induced by CFS than those given only one foot shock session, indicating an augmentation of fear and stress intensity. CFS after repeated foot shock, like foot shock per se, increased the DA metabolism in most of the brain regions except for the striatum and increased the 5-HT metabolism in the mPFC, nucleus accumbens, and amygdala. These results suggest that regional patterns of brain DA and 5-HT activation after physical and psychological stress depend on the intensity of that stress, although there are some differences between these stress; and that the more widespread activation of DA and 5-HT after more severe stress might relate to behavioral changes that reflect the augmentation of fear.     

Controllability and safety signals exert dissimilar proactive effects on nociception and escape performance.

In the present experiments we assess the ability of exteroceptive safety signals to proactively mimic shock controllability. In Experiment 1, animals were given escapable shock, yoked inescapable shock, restraint, or yoked shock with a stimulus coincident with shock offset on Day 1 and then given inescapable shock on Day 2. Safety signals attenuated the hypoalgesia following the first shock session. On Day 2, however, animals that had been preshocked with safety signals were not less hypoalgesic than those previously restrained. Conversely, shock controllability did not attenuate the hypoalgesia following the first session but proactively attenuated hypoalgesia during the second. Unlike animals preexposed to controllable shock, those given safety signals evidenced shuttle escape deficits 24 hr following the Day 2 inescapable shock treatment. Safety signals therefore failed to exert "immunization" effects. By employing identical preshock and shuttle test procedures, in Experiment 2 we demonstrated that safety signals completely block development of the escape deficit which otherwise results from the initial inescapable shock exposure. Thus, safety signals effectively reduce the impact of shock delivered in the same session but are ineffective in reducing the effect of subsequent shock. These results suggest that distinct processes underlie the effects of controllability and safety signals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Type of start box and goal box distinctiveness in self-punitive running of rats.

A total of 96 male Sprague-Dawley rats were first trained to escape shock in an alley by running to a safe goal box. In Exp I either a trapdoor-floored start box or a guillotine-door start box was used in different groups. In extinction, nonpunished and punished subgroups were tested in each of the start-box conditions. Punishment produced faster running speeds than nonpunishment (self-punitive effect) only with the trapdoor. The trapdoor start box was used in Exp II, and independent groups of Ss were trained to escape to a goal box that was either very dissimilar or similar to the shock area. Nonpunished and punished subgroups were extinguished in each goal box condition. Self-punitive running was more likely with the dissimilar goal box. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Escape deficits induced by uncontrollable foot-shock in recombinant inbred strains of mice

Although uncontrollable stressors reliably induce numerous behavioral disturbances, considerable interindividual variability exists in this respect. Inasmuch as genetic factors may be fundamental in determining vulnerability to stressor effects, the present investigation assessed alterations in escape performance following exposure to uncontrollable foot-shock in the BALB/cByJ and C57BL/6ByJ mice and seven recombinant inbred strains. Exposure to uncontrollable foot-shock disrupted shuttle escape performance in a strain-specific manner; however, any differences due to gender were not particularly remarkable. The profile of stressor effects in the recombinant strains (i.e., performance deficits greater, lesser or intermediate to the progenitor strains) suggest that the stressor effects on escape performance may be subserved by two or more genetic determinants. The findings are related to central mechanisms that may potentially account for strain differences.     

Dissociation of antinociception and escape deficits induced by stress in mice.

Six experiments (327 Swiss-Webster mice) assessed the conditions under which stress would induce antinociception in a subsequent hot-plate test. Both footshock and tail shock produced the antinociception. This effect was apparent with as little as a single shock trial. The magnitude of the antinociception was maximal following 15 shock presentations and was largely reduced after 60 shocks. In contrast to the results of R. L. Jackson et al (see record 1980-31880-001), whether stress was escapable was not a necessary feature needed to produce the antinociception. Moreover, the magnitude of the antinociception induced by stress was not enhanced in mice that had previously been exposed to stress. Finally, morphine (10.0, 20.0, and 30.0 mg/kg, ip) produced a pronounced antinociception but did not appreciably influence escape performance in a shuttle task in which performance was disrupted by inescapable shock. It is suggested that the antinociception and shuttle-escape deficits induced by uncontrollable shock are independent of one another. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of exposure to conditioned stimulus and control of its termination in the extinction of avoidance behavior.

Describes 2 experiments in which, following signaled shuttle box avoidance training, a total of 52 female Fischer344 rats were exposed to the conditioned stimulus (CS) during no-shock treatment trials and subsequently tested during extinction trials in which shock was also absent. In Exp I, Ss that could control the termination of the CS during treatment responded significantly more often during extinction than yoked partners that received the same pattern and duration of CS exposure but could not control its termination. Exp II revealed that the probability of responding during extinction was a decreasing function of the duration of CS exposure during treatment. Thus, in the absence of shock, both lack of control over CS termination and increasing CS exposure each independently facilitated the weakening of well-established avoidance responses. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Potentiation, overshadowing, and prior exposure to inescapable shock.

Four experiments are reported which explore the possibility that prior exposure to inescapable shock alters the way in which animals process information from responding during subsequent escape training. The stimulus consequences of responding were manipulated in each experiment. Rats received escapable shock, yoked, inescapable shock, or no shock prior to fixed ratio-2 (FR-2) shuttle escape training. A novel change in illumination following each shuttle response had opposite effects on inescapably shocked and control subjects. It dramatically improved the performance of inescapably shocked rats but impaired the performance of restrained subjects. The signal had no effect on escape trained animals. Response-produced auditory cues following each lever press on an FR-3 lever-press escape task were also observed to improve learning in inescapably shocked rats but to impair learning in restrained controls. The relation between lever pressing and the exteroceptive cue was manipulated. The exteroceptive cue enhanced learning in inescapably shocked rats when any two of the three required lever presses produced the cue. In contrast, the performance of restrained animals was impaired whenever the third response of the FR-3 produced the cue. Otherwise performance was unimpaired. The implications of these results are discussed with respect to the phenomena of potentiation and overshadowing, as well as to ways in which prior exposure to inescapable shock might alter information processing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Escape/avoidance responding in rats depends on strain and number of inescapable preshocks.

2 experiments examined escape-avoidance responding in a 1-way jump box following exposure to signaled, inescapable shock. In Exp I with 24 female Long-Evans rats, the occurrence of failures to escape and to avoid was an increasing function of the number of preshocks, over a range of 75-275, with a pronounced interference effect occurring after 225 and 275 preshocks. In Exp II with 10 Long-Evans (noninbred) and 10 Fischer (inbred) female rats, there were large differences between strains in failures both to escape and to avoid following 225 preshocks. Long-Evans Ss were severely retarded, whereas Fischer Ss were disrupted only during the initial trials. Findings demonstrate the importance of strain and number of preshocks in controlling the interference effect in rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Retardation of extinction of an escape response by prolonged, intense goal box shock.

Studied the effects of intense, response-contingent goal box shock on the extinction of a runway-escape response in 40 male albino rats by means of a 2?×?2 factorial design in which presence vs absence of goal box shock during escape training was crossed with the same factor during extinction. Of the 2 groups trained with shock in the goal box, the 1 shocked there during extinction exhibited dramatically enhanced resistance to extinction. The group not punished there extinguished more rapidly than any of the other 4 groups. The remaining 2 groups responded at levels between these 2 groups but did not differ from each other. Results are discussed in terms of various learning-theory mechanisms, such as conditioned fear and stimulus generalization, and with emphasis on similarities between the procedures of the present study and those extant "alley-shock" and "goal-shock" self-punitive designs. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Surgical treatment of morbus Menière (author''s transl)

CFW mice were injected with methylmercury hydroxide (1, 2, 3, 5 or 10 mg/kg as mercury) on Day 8 of gestation. Mice treated with 3, 5 or 10 mg/kg averaged 1/3 fewer pups than controls. Pups from these treated animals weighed less than controls and the weight differences persisted through weaning but were no longer significant at 56 days of age. Mice exposed to methylmercury in utero showed significant differences from controls in their behavior in a 2-way active avoidance shuttle box and in a punishment situation but not when tested in an open field, a water escape runaway or a conditioned suppression paradigm. Neither the mothers nor progeny of the mice exposed prenatally to methylmercury showed bahavioral deficits.     

Differential effects of forward or simultaneous conditioned stimulus-unconditioned stimulus intervals on the defensive behavior system of the Norway rat (Rattus norvegicus).

To test several predictions derived from a behavior-systems approach, the authors assessed Pavlovian fear conditioning in rats after 30 trials of forward, simultaneous, or unpaired training. Direct evidence of conditioned fear was collected through observation of flight and freezing reactions during presentations of the conditioned stimulus (CS) alone. The authors also tested the CS's potential to reinforce an instrumental escape response in an escape-from-fear paradigm. On the one hand, rats that received forward training showed conditioned freezing, but no conditioned flight was observed. On the other hand, rats that received simultaneous training showed conditioned flight, but no conditioned freezing was observed. Rats that received either forward or simultaneous pairings showed instrumental learning of the escape-from-fear response. Implications for several theories of Pavlovian conditioning are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned fear and postshock emotionality in vicious circle behavior of rats.

Gave 64 female hooded Long-Evans rats 15 shock-escape trials in a runway (1 trial/day), followed by 30 extinction trials. Half of the Ss received regular extinction treatment, while the others received a punishing shock if they ran. The Ss' level of activity (or freezing) before the trial was used as an index of conditioned fear. In acquisition, these shocked Ss were less active before the trial than 56 additional Ss receiving identical treatment, but without shock. During extinction, punished Ss both ran longer and showed less pretrial activity. This directly supports the vicious circle hypothesis that punishment for running maintains the fear motivating the running. When postshock emotionality was induced before a trial, it tended to suppress vicious circle behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)