Individual differences in vulnerability to inescapable shock in rats.

The present study determined whether individual differences in neophobia during an open-field pretest predict vulnerability to inescapable electric shock, as measured by 2 tests of learned helplessness in rats. Shuttle-escape latencies and saccharin finickiness increased across groups that had received increasing numbers of inescapable shocks 24 hr earlier. Dispersion in the test measure as well as the percentage of variance explained by pretest neophobia were greater when no or few shocks were delivered in the interpolated stress phase. Pretest neophobia was positively related to stress vulnerability in both tests under these conditions. Further increments in stressor severity overwhelmed even the most stress-resistant rats, thereby decreasing dispersion in the test measure and eliminating the predictive value of pretest neophobia. This pattern of outcomes was more robust for the shuttle-escape measure of helplessness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dissociation of long-term analgesia and the shuttle box escape deficit caused by inescapable shock.

Previous studies indicate that inescapably shocked rats perform poorly on a 2-way shuttlebox escape task 24 hrs after shock. Because inescapably shocked rats become analgesic upon reexposure to a small amount of shock 24 hrs after inescapable shock (IS), they are likely to be analgesic during the shuttlebox escape task. Ss receiving an equivalent amount of escapable shock display neither the escape deficit nor the analgesia. Both the analgesia and the escape deficit respond in a similar fashion to the manipulation of a variety of other variables. These findings have led to the suggestion that the analgesia (long-term analgesia) may cause the IS-produced escape deficit. However, the present 2 experiments with 72 male albino rats demonstrated that 2 pituitary manipulations that completely eliminate the analgesia have no effect on the escape deficit. Both hypophysectomy and dexamethasone administration blocked the analgesic consequences of IS but did not reduce the magnitude of the escape deficit. Therefore, the long-term analgesia produced by IS does not cause the deficit in shuttlebox escape performance displayed by inescapably shocked rats. Results indicate that the pituitary is not essential in the production of this escape deficit. (47 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of naltrexone and signaling inescapable electric shock on nociception and gastric lesions in rats.

Two experiments, with 144 male Long-Evans hooded rats, examined the antinociceptive effects of signaled shock and its physiological underpinnings. In Exp I, Ss were exposed to 1 of 3 shock conditions: no shock, unsignaled shock, and signaled (by a 10-sec, 1,000-Hz tone) shock. In each condition, Ss were tested hourly in the absence of tones for nociception, with vocalization to shock used as the behavioral measure. Ss receiving signaled shocks had stomach ulcer scores intermediate between those of no-shock and unsignaled shock Ss. Signaled-shock Ss also displayed a pronounced vocalization antinociception effect. This suggested that signaled shock may be less aversive. Exp II investigated a possible role of endogenous opiate peptides in these effects. Ss received hourly injections of either the opiate antagonist naltrexone (7 mg/kg, ip) or saline. There were no significant effects of naltrexone on either stomach pathology or nociception scores. The same effects of signaled shock were obtained as in Exp I. It is concluded that the role of endogenous opiates in the effects of signaled shock seen here is minimal. (38 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

Ventromedial septal lesions in rats reduce the effects of inescapable shock on escape performance and analgesia.

In 2 experiments with 104 male Sprague-Dawley rats, lesions of the ventromedial septum (VMS) reduced or eliminated several effects of exposure to inescapable shock, but lesions of the dorsolateral septum did not. Exp I demonstrated that VMS lesions reduced the loss in body weight produced by inescapable shock and eliminated the subsequent (24 hrs later) interference with escape performance (learned helplessness). Exp II demonstrated that VMS lesions reduced the analgesia that occurs immediately following inescapable shock and the analgesia reinstated by exposure to escapable shock 24 hrs later. Findings indicate that VMS lesions reduce several responses to inescapable shock and suggest the possibility that all of these effects may reflect a unitary deficit. It is hypothesized that VMS lesions reduce these effects of exposure to inescapable shock either by reducing the ability of the rats to learn that their responses and shocks were uncorrelated or by reducing the emotional impact of this lack of correlation. (52 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cross-motivational effects of inescapable shock are associative in nature.

An appetitive choice discrimination test was used to assess the relative contribution of activity and associative effects of inescapable shock (IS) in a cross-motivational paradigm. A 2-response nosepoke test was used following IS treatment. In Exp I, male Holtzman rats demonstrated separate associative and activity effects of IS. Ss exposed to IS made more incorrect responses than controls and were lower in activity. Exp II demonstrated that these effects resulted from the uncontrollability of the shock, not from shock exposure per se. In Exp III, residual effects of IS were investigated by exposing Ss to discrimination reversals. On these tests, shocked Ss showed performance inferior to nonshocked controls, a result indicating that the effects of IS were not completely reversed by experience with contingent reward in the discrimination task. Results suggest that associative factors play a more important role than activity reduction in mediating the effects of IS, at least when these are measured in an appetitive context. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of fear in mediating shuttle escape learning deficit produced by inescapable shock.

The relation between the shuttlebox escape deficit produced by prior inescapable shock (IS) and fear during shuttlebox testing as assessed by freezing was investigated in rats. IS rats learned to escape poorly and were more fearful than either escapably shocked subjects or controls, both before and after receiving shock in the shuttlebox. However, fear and poor escape performance did not covary with the manipulation of variables designed to modulate the amount of fear and the occurrence of the escape deficit. A 72-hr interval between IS and testing eliminated the escape deficit but did not reduce preshock freezing. Diazepam before testing reduced both preshock and postshock fear in the shuttlebox but had no effect on the escape deficit. Naltrexone had no effect on fear but eliminated the escape deficit. This independence of outcome suggests that the shuttlebox escape deficit is not caused by high levels of fear in IS subjects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of response restriction during exposure to inescapable shock upon subsequent one-way and shuttle-avoidance performance in rats.

Investigated the effects of signaled inescapable shock on subsequent avoidance performance in 3 experiments with male Holtzman rats (N = 188). Exp I indicated that prior shock exposure (PSE) facilitated 1-way and shuttle avoidance. When Ss were preshocked in a harness so that free mobility was not possible, the facilitative effects of PSE on shuttle, but not 1-way avoidance performance, were largely reduced. Exp II indicated that activity during CS periods following PSE was greater among unrestrained than restrained Ss. Exp III showed that immobilization via injection of succinylcholine chloride did not affect the facilitative effects of PSE relative to that of Ss preshocked in a harness. Results are interpreted in terms of response repertoire changes produced by PSE in conjunction with the response requirement of the avoidance task. (French summary) (17 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stress and adenosine: II. Adenosine analogs mimic the effect of inescapable shock on shuttle-escape performance in rats.

Examined, in 3 experiments involving 208 male rats, the role of adenosine regulation in escape deficits produced by earlier exposure to inescapable shock in rats (learned helplessness). Adenosine analogs injected before escape testing mimicked the effect of earlier inescapable shock, with the magnitude of the deficit varying with dose and drug specificity for A? adenosine receptors. Agonist-induced and stress-induced escape deficits were eliminated by pretest treatment with the centrally acting adenosine receptor antagonist theophylline but not the peripheral antagonist 8-[p-sulfophenyl]-theophylline. Finally, preexposure to an ineffective number of inescapable shocks interacted in synergy with an ineffective pretest injection of adenosine agonist to maximize deficits in escape performance. These data implicate energy regulation and a central compensatory action by adenosine in the aspects of helplessness related to onservation–withdrawal. (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)     

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)     

Enhanced bradycardia induced by beta-adrenoceptor antagonists in rats pretreated with isoniazid

Recent studies indicate that the midcycle gonadotropin surge in the human occurs without an increase in hypothalamic gonadotropin-releasing hormone (GnRH) pulse frequency. In addition, previous studies employing a GnRH antagonist to provide a semiquantitative estimate of endogenous GnRH secretion suggest that the overall amount of GnRH secreted is decreased at the time of the surge. To investigate the hypothesis that a normal gonadotropin surge can be generated in the human with a decreased amount of GnRH at the midcycle, 7 GnRH-deficient subjects underwent two cycles of a physiologic regimen of intravenous pulsatile GnRH therapy. In the control cycle, 75 ng/kg/bolus of GnRH, a dose known to be sufficient for folliculogenesis, was administered throughout the cycle, using physiological frequencies. In a second cycle, the bolus dose of GnRH was decreased by one-half log order to 25 ng/kg just prior to the luteinizing hormone surge and returned to 75 ng/kg after documented ovulation. All cycles were ovulatory. The peak luteinizing hormone level (77.4 +/- 9.7 vs. 67.5 +/- 17.6 IU/l) did not differ between the control and decreased GnRH cycles. There was no difference in the peak serum estradiol level (475.8 +/- 144.1 vs. 493.2 +/- 93.0 pg/ml), follicular phase length (15.0 +/- 1.3 vs. 14.8 +/- 0.6 days), or progesterone level (22.4 +/- 5.1 vs. 34.8 +/- 5.7 ng/mg) on day 6 of the luteal phase in the control and decreased GnRH cycles, respectively. Three pregnancies were achieved in each of the control and reduced GnRH cycles. We conclude that a decreased overall amount of GnRH generates a normal midcycle gonadotropin surge and has no significant impact on luteal phase adequacy or fertility. These results provide further evidence that a decrease in endogenous hypothalamic GnRH secretion may occur at the midcycle in normal women. This study also provides evidence that the GnRH requirements for normal follicular and luteal phase dynamics may well be greater than those required for generation of a normal midcycle gonadotropin surge and ovulation in women.     

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)     

Chlordiazepoxide microinjected into the region of the dorsal raphe nucleus eliminates the interference with escape responding produced by inescapable shock whether administered before inescapable shock or escape testing.

Systemic administration of benzodiazepines before exposure to inescapable shock (IS) blocks the enhanced fear conditioning and escape learning deficits that follow exposure to IS, whereas administration before the subsequent behavioral testing eliminates the enhanced fear but not the interference with escape (N?=?44 male rats). The failure of benzodiazepines to reduce the IS-produced escape learning deficit when given before testing is inconsistent with a recent proposal that interference with escape is mediated by an IS-induced sensitization of dorsal raphe nucleus (DRN) activity. The present experiments demonstrate that chlordiazepoxide will block both the enhancement of fear and interference with escape responding when given before either IS or testing if microinjected in the region of the DRN. This suggests that systemic benzodiazepines fail to block escape deficits when given before testing because action at a site distant from the DRN counters the effect of the drug at the DRN. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Long-term analgesic reaction in attacked mice.

Four experiments were designed to characterize long-term analgesic (LTA) reaction in attacked mice. In Experiment 1 we showed that analgesic reaction in DBA/2 mice, induced by the stress of being attacked (30 or 50 bites), is reinstated upon reexposure to seven bites 24 hr later. The magnitude of the LTA response depended on the level of analgesia on Day 1 and was smaller than the original response. In Experiment 2 we showed that LTA was prevented by naloxone or beta-chlornaltrexamine given before exposure (50 bites) on Day 1. Results of Experiment 3 revealed that naloxone or beta-chlornaltrexamine injected before reexposure to seven bites on Day 2 antagonized LTA measured 10 min, but not 1 min, after reexposure. In Experiment 4 we showed that morphine substituted for being attacked on Day 1 failed to produce LTA. We concluded that pain inhibitory mechanisms remain in a state of increased readiness for at least 24 hr after attack stress and that activation of opioid systems is necessary but not sufficient to produce LTA, a response that is only partly sensitive to opioid antagonists. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Escape deficits following inescapable shock: The role of contextual odor.

Three experiments, with 192 male albino rats, examined the role of contextual odor in mediating deficits in escape performance produced by pretreatment with inescapable shock. Impaired leverpress performance (Exp I) and shuttle-escape performance (Exp II) were observed when the pretreatment and test chambers were odorized by previously shocked conspecifics. These deficits were eliminated in both experiments when the test chambers were thoroughly cleaned. Exp III determined whether the same odor must be present during pretreatment and testing, or whether mere exposure to a fear pheromone is sufficient to impair test performance. Shuttle escape was impaired only when the same odor was present in the pretreatment and test chambers. Results indicate that an odor common to the pretreatment and test chambers mediates impaired escape performance and suggests that other types of deficits observed following inescapable shock may also be mediated by such contextual cues. (36 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hematopoietic changes in rats after inescapable and escapable shocks

The key hypothesis of the study was that hospital pharmacies under the pressure of managed care would be more likely to adopt process innovations to assure less costly and more cost-effective provision of care. We conducted a survey of 103 hospitals and analyzed secondary data on cost and staffing. Compared to the size of the reduction in length of stay, changes in the way that a day of care is delivered appear to be minor, even in areas with substantial managed care share. The vast majority of hospitals surveyed had implemented some form of therapeutic interchange and generic substitution. Most hospitals used some drug utilization guidelines, but as of mid 1995 these were not yet important management tools for hospital pharmacies. To our knowledge, ours was the first survey to investigate the link between hospital formularies and use of cost-effectiveness analysis. At most cost-effectiveness was a minor tool in pharmaceutical decision making in hospitals at present. We could determine no differences in use of such analyses by managed care market share in the hospital's market share. One impediment to the use of cost-effectiveness studies was the lack of timeliness of studies. Other stated reasons for not using cost-effectiveness analysis more often were: lack of information on hospitalized patients and hence on the potential cost offsets accruing to the hospital: lack of independent sponsorship, and inadequate expertise in economic evaluation.     

Opiate modulation of the active and inactive components of the postshock reaction: Parallels between naloxone pretreatment and shock intensity.

In 4 experiments with 96 female Long-Evans rats, electric footshock elicited an immediate burst of activity followed by a period of immobility. Naloxone HCl (4 mg/kg, ip) enhanced both of these postshock reactions. Naloxone's effects on the active and inactive components of the postshock reaction paralleled those of increasing shock intensity, which suggests that the drug caused these results by enhancing the perceived intensity of shock. The facilitatory effects of naloxone on the active and inactive reactions to shock appear to be specific to nociceptive stimuli, as naloxone decreased the activity burst elicited by a nonnociceptive startling stimulus and had no effect on the freezing that followed that nonnociceptive stimulus. Naloxone could accomplish its alteration of perceived intensity by antagonizing endogenous opioid analgesic systems. However, as hypophysectomy did not block the drug's action, the effects are not mediated by pituitary opioids. (36 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fear conditioned with escapable and inescapable shock: Effects of a feedback stimulus.

Four experiments, with 140 male Fischer rats, compared the level of fear conditioned with escapable and inescapable shock. In Exps I and II, master Ss that had received 50 unsignaled escapable shocks were less afraid of the situation where the shock had occurred than were yoked Ss that had received inescapable shocks. Comparable results were found in Exps III and IV, which used freezing as an index of fear of a discrete CS that had been paired with shock. Control per se was not necessary to produce the low level of fear seen in the master Ss. Yoked groups receiving a feedback signal at the time the master made an escape response showed a low level of fear that was comparable to that of the masters and significantly less than that seen in the yoked Ss without feedback. In addition, there were strong suggestions that control and feedback exert their effects through the same or highly similar mechanisms. Possible explanations for how control and the exteroceptive feedback signal produce this effect are discussed. (35 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Exposure to inescapable stress persistently facilitates associative and nonassociative learning in rats.

The present study examined the proactive effects of inescapable stress on aversive Pavlovian conditioning. Stressed rats were restrained and exposed to 90 1-mA tailshocks. Twenty-four hours later, all rats were exposed to 10 conditioned stimuli (CS; 350 ms of white noise at 85 dB). Rats then received either paired training in which the CS coterminated with a 100-ms, 0.7-mA periorbital shock or the same stimuli presented in an explicitly unpaired fashion. After the unpaired exposures, these rats were also exposed to paired training. Previously stressed rats exhibited persistent sensitization to the white-noise stimulus. Stressed rats exposed to unpaired stimuli, and no longer exhibiting a sensitized response, acquired the eyeblink conditioned response at a facilitated rate when these stimuli were presented in a paired fashion. These results also demonstrate that the effect of stress on classical conditioning is long-lasting, in excess of 48 hr. (PsycINFO Database Record (c) 2010 APA, all rights reserved)