Potentiation of the acoustic startle response by a conditioned stimulus paired with acoustic startle stimulus in rats

The hypothesis that the standard acoustic startle habituation paradigm contains the elements of Pavlovian fear conditioning was tested. In a potentiated startle response paradigm, a startle stimulus and a light conditioned stimulus (CS) were paired. A startle stimulus then was tested alone or following the CS. Freezing behavior was measured to index conditioned fear. The startle response was potentiated on CS trials, and rats froze more in CS than in non-CS periods. In Experiment 1, response to a previously habituated, weak startle stimulus was potentiated. In Experiment 2, response to the same stimulus used as the unconditioned stimulus (US) in training was potentiated. This CS-potentiated response retarded the course of response decrements over training sessions as compared with an explictly unpaired control group. Conditioned fear is a standard feature of this habituation paradigm, serves to potentiate the startle response, and provides an associative dimension lacking in the habituation process per se.     

Measurement of acoustic startle response in mice

Apparatus for measurement of acoustic startle response in mice is described. The technique utilizes a spring suspended lever, commercially available strain-gauge transducer, and polygraph. Individual startle responses are recorded as upward (flexion) and downward (extension) pen deflections, the force of either component being linearly related to the amplitude of the vertical pen deflections. The apparatus, with minor modifications, may be used to measure startle responses in larger rodents.     

Effect of exposure to lithium-paired or amphetamine-paired saccharin solution on open arm avoidance in an elevated plus maze

Recent evidence suggests that drug-induced conditioned taste avoidance may be mediated by conditioned fear (e.g., Parker, 2003). The experiments reported here evaluated the effect of exposure to a drug-paired flavor on open arm exploration in an elevated plus maze (EPM), a measure of fear. When rats were tested on a familiar (trial 2) EPM, but not on a novel (trial 1) EPM, prior exposure to a lithium-paired saccharin solution enhanced open arm activity relative to saline-paired saccharin. On the other hand, when rats were exposed to lithium-paired saccharin during plus maze exposure, they displayed suppressed open arm activity relative to unpaired controls when tested in a familiar maze. The pattern of results was specific to the conditional affective properties of the taste, because exposure to unconditional sickness produced by administration of lithium, and unconditionally unpalatable quinine solution did not produce this pattern. These results were interpreted in terms of the opponent process model of motivation; that is, exposure to a lithium-paired flavor elicits conditioned fear which is immediately followed by conditioned relief when the exposure is terminated. On the other hand, exposure to an amphetamine-paired flavor either before or during EPM testing enhanced open arm exploration. Since the strength of taste avoidance did not differ among amphetamine and lithium conditioned rats, these results provide further evidence that the nature of a saccharin-lithium association differs from that of a saccharin-amphetamine association.     

Ontogeny of the adrenal response to (+)-methamphetamine in neonatal rats: the effect of prior drug exposure

We examined the ontogeny of the corticosterone response to (+)-methamphetamine in neonatal rats. In experiment-1, animals were injected with 10 mg/kg of (+)-methamphetamine or saline and plasma corticosterone levels were examined in separate groups 30 or 105 min later on postnatal day (P) 1, 3, 5, 7, 9, 11, 13, 15, 17, or 19. The adrenal response to methamphetamine was best described by a U-shaped function with the nadir of corticosterone release occurring between P7 and P13. Experiment-2 was similar except that the effect of four consecutive days of exposure to (+)-methamphetamine (four times daily at 2 h intervals with 10 mg/kg) was assessed with a single final dose early on the fifth day (i.e. P1-5, 3-7, 5-9, 7-11, 9-13, 11-15, 13-17, 15-19). The 30 min corticosterone response after multiple methamphetamine doses was augmented compared to single exposures, with the exception of the two earliest dosing intervals ending on P5 and P7, where the responses were lower. In addition, at 105 min, the levels of corticosterone were attenuated relative to a single drug administration. With the exception of animals receiving methamphetamine from P15 to P19, thymus weights were unaffected. The data demonstrate that (+)-methamphetamine is a robust activator of corticosterone release in developing animals and this release is extensively modified by age and previous drug exposure.     

Modification of the rat's acoustic startle response by antecedent visual stimulation.

Male hooded and albino rats were exposed to a light flash followed at various temporal intervals by a startle-eliciting 117 db. (re 20 muN/m2) burst of white noise. The visual stimulus engendered startle response inhibition (maximally when the lead time was 64-250 msec) as well as startle response latency reduction (maximally when the lead time was 2-8 msec). The temporal functions for the effects of visual stimuli paralleled those previously reported for startle modification by acoustic events. Further study revealed that, given optimal lead times, inhibition is produced reliably by weaker visual stimuli (3 X 10-6 cd-sec/cm2) than latency reduction (3 X 10-4 cd-sec/cm2). This differential sensitivity to visual stimuli is also analogous to previously reported findings for events in the acoustic environment. It reveals that the neural mechanisms that mediate latency reduction and inhibition can be engaged by either acoustic or visual stimulation.     

Influence of long-term sensitization on long-term habituation of the acoustic startle response in rats: central gray lesions, preexposure, and extinction

The relation between long-term decrements of the acoustic startle response in rats and the development of freezing behavior during habituation training was examined. Freezing behavior developed over the initial trials of habituation training, and the rate of long-term response decrements was found to be inversely related to the development of freezing. Manipulations (neurological or behavioral) that either reduced the level of freezing or retarded its development promoted startle response decrements. In Experiment 1, rats receiving electrolytic lesions of the ventrolateral periaqueductal gray demonstrated both accelerated long-term startle response decrements and retarded development of freezing behavior. In Experiment 2, preexposure to the startle apparatus (i.e., latent inhibition) accelerated long-term startle decrements and inhibited development of freezing. In Experiment 3, exposure to the startle apparatus following initial habituation training (i.e., extinction) reduced both freezing behavior and startle response amplitudes. The results are discussed in terms of the influence of Pavlovian fear conditioning on long-term habituation of the acoustic startle response.     

Effect of manipulating the risetime of an acoustic stimulus on two protective reflexes: cardiac defense and motor startle

Effect of manipulating the risetime of an acoustic stimulus on two protective reflexes: cardiac defense and motor startle. The risetime is a parametric characteristic of the eliciting stimulus frequently used to differentiate among psychophysiological reflexes. The aim of the present study was to examine the effect of manipulating the risetime of an acoustic stimulus on two protective reflexes: cardiac defense and motor startle. 100 participants underwent a psychophysiological reactivity test to five presentations of an intense acoustic stimulus (105 dB white noise) under one of five risetime conditions: 0, 24, 48, 96, and 240 ms. Total energy of the stimulus was controlled by increasing the base duration of the stimulus (1000 ms) by one third of the risetime. Results showed that risetime significantly affected motor startle but not cardiac defense. Startle amplitude decreased linearly with increasing risetime after 24 ms. On the other hand, repetition of the stimulus significantly affected cardiac defense but not motor startle. These results question the traditional differentiation between startle and defense based on risetime.     

Formation of taste aversions in rats following prior exposure to sickness

Findings from the present experiments extend those of earlier studies and show that rats form weaker conditioned taste aversions if they are exposed to a sickness-inducing agent prior to a single training trial. The present experiments appear to rule out the possible confounding factors that, during pretraining, (1) animals became addicted to the drugs that were intended to induce sickness during training, (2) drug tolerances were created and hence reduced the effectiveness of the same or different sickness-inducing agents used to induce sickness during training, or (3) associations between other stimuli and sickness were formed and interfered with or blocked the formation of subsequent taste aversions. It was concluded that the associative capacity of sickness can be reduced through pre-exposure.     

Similar effects of attention directed to acoustic and tactile stimuli on prepulse inhibition of acoustic startle

Prepulse inhibition (PPI) is assumed to index automatic and controlled processing. In three experiments (n= 32, 22, and 30) participants were asked to judge the duration of a prepulse in comparison with a stimulus presented 4000 ms before the prepulse. A distracter was presented simultaneously with the prepulse to increase the cognitive demands of the task. PPI was assessed at stimulus onset asynchronies (SOAs) of 30-150 ms, and 420 ms. The prepulse was either a tone (60 dB) or a tactile stimulus (21 kPa), and startle was elicited by 95 dB white noise. Directing attention to the prepulse increased PPI at SOAs of 60 ms and longer in all experiments, but the sensory modality to which attention was directed played only a minor role. We conclude that directing attention to both acoustic and tactile prepulses increased PPI.     

Proactive sensitizing effects of acute stress on acoustic startle responses and experimentally induced colitis in rats: relationship to corticosterone

In humans, some individuals develop a syndrome after trauma (post-traumatic stress disorder, PTSD) characterized by increased startle responses and lower than normal cortisol secretion. We explored a rat model using the acoustic startle response (ASR) as a behavioral indicator of the effect of a short series of shocks. Because gastrointestinal disorders have been associated with prior stress, we also studied the rats' vulnerability to a chemically-induced colitis. After initial blood sampling, 12 rats were exposed to ten 1 mA 5 s foot-shocks while 12 rats served as controls. Nineteen days later the rats were tested for ASR. Thirty trials (10 trials at each of 95, 105, and 115 dB, pseudo-randomized) were given. After exposure for 6 days to dextran sulphate sodium in their drinking water, the rats were killed and the colons examined for erosions. Shocked rats showed greater startle responses and more colonic erosion than unshocked rats, but the shock effects were significant only for animals with low initial plasma corticosterone levels. Shocked rats also showed higher levels of granulocyte marker protein (GMP) in their faeces. These results suggest that low corticosterone secretion may represent a marker for vulnerability to long term effects of shocks as indicated by increased startle responses and colonic pathology.     

Meditation and the startle response: a case study

The effects of two kinds of meditation (open presence and focused) on the facial and physiological aspects of the defensive response to an aversive startle stimulus were studied in a Buddhist monk with approximately 40 years of meditation experience. The participant was exposed to a 115-db, 100-ms acoustic startle stimulus under the 2 meditation conditions, a distraction condition (to control for cognitive and attentional load) and an unanticipated condition (startle presented without warning or instruction). A completely counterbalanced 24-trial, single-subject design was used, with each condition repeated 6 times. Most aspects of the participant's responses in the unanticipated condition did not differ from those of a comparison group of 12 age-matched male controls. Both kinds of meditation produced physiological and facial responses to the startle that were smaller than in the distraction condition. Within meditation conditions, open presence meditation produced smaller physiological and facial responses than focused meditation. These results from a single highly expert meditator indicate that these 2 kinds of meditation can differentially alter the magnitude of a primitive defensive response.     

Acute exposure to a novel stressor further reduces the habituated corticosterone response to restraint in rats

The present study sought to identify dishabituation of the hypothalamic-pituitary-adrenal(HPA) axis response to different psychological stressors. Young adult male Sprague Dawley rats were exposed to five, 1 h sessions of restraint stress on five consecutive days. On the sixth day, and 2 h before additional exposure to restraint, animals were subjected to 30 min of a small (27cm square), elevated open field stressor (pedestal), which served as the dishabituating stimulus. We predicted HPA axis response dishabituation in chronically restrained rats exposed to the novel pedestal. Rats which underwent five days of restraint stress showed significantly blunted plasma corticosterone levels to restraint (habituation) as compared to restraint-nai've rats. However, rats which underwent five sessions of restraint responded with an enhanced habituation response when confronted with restraint shortly after exposure to the novel pedestal. Instead of HPA axis response dishabituation, we observed enhanced habituation. Subsequent experiments determined that a 1.25 mgkg corticosterone injection could substitute for pedestal exposure to produce enhanced restraint habituation.Combined treatment with both the glucocorticoid receptor antagonist RU40555 (30 mgkg)and the mineralocorticoid receptor antagonist RU283 18 (50 mgkg) blocked the expression of enhanced habituation after pedestal exposure. Thus, the delayed corticosterone negative feedback produced by novel stress led to enhanced expression of corticosterone response habituation.     

Adaptation to auditory motion in the horizontal plane: Effect of prior exposure to motion on motion detectability

Thresholds for auditory motion detectability were measured in a darkened anechoic chamber while subjects were adapted to horizontally moving sound saurces of various-velocities. All stimuli were 500-Hz lowpass noises presented at a level of 55 dBA. The threshold measure employed was the minimum audible movement angle(MAMA)—that is, the minimum angle a horizontally moving sound must traverse to be just discriminable from a stationary sound. In an adaptive, two-interval forced-choice procedure, trials occurred every 2-5 sec (Experiment 1) or every 10–12 sec (Experiment 2). Intertrial time was “filled” with exposure to the adaptor—a stimulus that repeatedly traversed the subject’s front hemifield at ear level (distance: 1.7 m) at a constant velocity (?150°/secto + 150°/sec)during a run. Average MAMAs in the control condition, in which the adaptor was stationary (0°/sec), were 2.4° (Experiment 1) and 3.0° (Experiment 2). Three out of 4 subjects in each experiment showed significantly elevated MAMAs (by up to 60%), with some adaptors relative to the control condition. However, there were large intersubject differences in the shape of the MAMA versus adaptor velocity functions. This loss of sensitivity to motion that most subjects show after exposure to moving signals is probably one component underlying the auditory motion aftereffect (Grantham, 1989), in which judgmentsof the direction-afmoving sounds are biased in the direction opposite to that of a previously presented adaptor.     

Effect of a novel experience prior to training or testing on retention of an inhibitory avoidance response in mice: involvement of an opioid system

These experiments examined the effects of a novel experience prior to training or retention testing on 24-h retention of an inhibitory avoidance response in mice. The experiments were based on previous evidence that novel training experiences release hypothalamic beta-endorphin. When given 1 h prior to training, the novel experience (clinging to the wire-mesh ceiling and exploring a small box) attenuated the memory-enhancing effects of post-training administration of naloxone as well as the enhancing effects of beta-endorphin administered prior to the retention test. The novel experience given prior to training did not block the enhancing effects of post-training administration of epinephrine. beta-Endorphin and the novel experience both enhanced retention performance when administered 1 h (as well as 3 but not 6 h) prior to the retention test. The enhancement found with both treatments was blocked by simultaneous administration of naloxone or by administration of propranolol a few minutes prior to the retention test. The findings of these experiments are consistent with the view that the effects of the novel experience are due to a release of endogenous beta-endorphin and provide additional evidence that the effects, on retention, of naloxone given post-training and beta-endorphin given prior to a retention test, are based on training-induced release of beta-endorphin.     

Stuttering and sensory gating: a study of acoustic startle prepulse inhibition

It was hypothesized that stuttering may be related to impaired sensory gating, leading to overflow of superfluous disturbing auditory feedback and breakdown of the speech sequence. This hypothesis was tested using the acoustic startle prepulse inhibition (PPI) paradigm. A group of 22 adults with developmental stuttering were compared with controls regarding the degree of PPI. No significant differences were found between the stuttering adults and the control group; the groups showed similar means and distribution. Likewise, no relation between the degree of PPI and the effect of altered auditory feedback on stuttering was found. In summary, the results of the study indicate that there is no relation between stuttering and PPI.