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 prior exposure to a lithium- and an amphetamine-paired flavor on the acoustic startle response in rats

The experiments reported here evaluated the hypothesis that an amphetamine-paired flavor elicits conditioned fear-arousal, whereas a lithium-paired flavor elicits conditioned nausea-disgust by examining the effect of prior flavor exposure on an acoustic startle reaction (ASR). Exposure to a lithium-paired flavor by intraoral infusion, either immediately prior to a startle session (Experiment 1) or during a startle session (Experiments 2 and 3), resulted in a blunted ASR. In contrast, intraoral infusion of an amphetamine-paired flavor resulted in a potentiated ASR. The blunted ASR produced by exposure to a lithium-paired flavor dramatically reversed to a potentiated ASR when rats were pretreated with the antiemetic drug ondansetron prior to the saccharin-lithium pairing (Experiment 3). The findings shed light on a mechanism by which rewarding drugs produce conditioned taste avoidance in rats.     

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.     

Startle responding and context conditioning

The possibility that acoustic startle stimuli could support a conditional response (freezing) to contextual stimuli was investigated. Rats were exposed to three acoustic startle stimuli on the first day, and one on the second day. On day 1, 20 rats received naloxone pretreatment and another 20 received saline (placebo) pretreatment. Half of each group received a high-intensity acoustic stimulus, the other half a low-intensity acoustic stimulus. Both the higher stimulus intensity and the naloxone pretreatment led to greater freezing behavior during the 3-minute test period before the single startle stimulus on day 2. These findings support the notion that increased actual or perceived intensity of the acoustic startle stimulus increases conditioning to contextual stimuli as indexed by freezing behavior.     

Prepulse effects on magnitude estimation of startle-eliciting stimuli and startle responses

The present studies investigated the relationship between prepulse effects on the modification of the brainstem startle reflex and magnitude estimates of startle-eliciting stimuli. In Experiment 1, startle eyeblink responses were elicited in 24 students, half of whom were instructed to estimate the loudness of the startle stimulus (actual intensities of 80, 90, and 100 dB) and half of whom were instructed to estimate the magnitude of their eyeblink. When weak acoustic prepulses preceded the startle-eliciting stimulus, eyeblink amplitude was inhibited, and estimates of response magnitude decreased, but estimates of startle stimulus magnitude decreased only when 100-dB startle stimuli were presented. In Experiment 2, the same startle stimuli were preceded on some trials by a vibrotactile prepulse to the hand. In conditions in which startle amplitude was inhibited, startle stimulus magnitude estimates were not affected. This suggests that the effect of acoustic prepulses on 100-dB startle stimuli in Experiment 1 may have been due to loudness assimilation, an effect independent of the prepulse inhibition of startle responding.     

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.     

Neural systems involved in fear and anxiety measured with fear-potentiated startle

A good deal is now known about the neural circuitry involved in how conditioned fear can augment a simple reflex (fear-potentiated startle). This involves visual or auditory as well as shock pathways that project via the thalamus and perirhinal or insular cortex to the basolateral amygdala (BLA). The BLA projects to the central (CeA) and medial (MeA) nuclei of the amygdala, which project indirectly to a particular part of the acoustic startle pathway in the brainstem. N-methyl-D-aspartate (NMDA) receptors, as well as various intracellular cascades in the amygdala, are critical for fear learning, which is then mediated by glutamate acting in the CeA. Less predictable stimuli, such as a long-duration bright light or a fearful context, activate the BLA, which projects to the bed nucleus of the stria terminalis (BNST), which projects to the startle pathway much as the CeA does. The anxiogenic peptide corticotropin-releasing hormone increases startle by acting directly in the BNST. CeA-mediated behaviors may represent stimulus-specific fear, whereas BNST-mediated behaviors are more akin to anxiety. NMDA receptors are also involved in extinction of conditioned fear, and both extinction in rats and exposure-based psychotherapy in humans are facilitated by an NMDA-partial agonist called D-cycloserine. ((c) 2006 APA, all rights reserved).     

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.     

Acoustic startle in maltreated children

We investigated the eyeblink component of acoustic startle reactions in maltreated children. Previous research indicates that acoustic startle is enhanced in adult males with posttraumatic stress disorders (PTSD) whereas findings on women with PTSD have been inconsistent. In accord with the only previous report for children with PTSD, we found that maltreated boys, particularly those who had been physically abused, responded to increases in startle probe loudness with smaller increments in amplitude of startle eyeblink and smaller reductions in blink latency than did comparison boys. Results for girls were inconsistent: younger maltreated girls had smaller startle amplitude and slower onset latency than controls, whereas older maltreated girls exhibited the opposite pattern.     

Inhibition of acoustic startle using different mechanoreceptive channels

In this experiment, we investigated the impact of vibrotactile prepulse frequency and intensity on the acoustically elicited startle response in humans. Mechanoreceptive channels differing in their sensitivity to transient stimulation have been identified in the skin. The Pacinian channel is optimally sensitive to vibrations at approximately 300 Hz and is specialized for the detection of stimulus transients, whereas the non-Pacinian I and III channels are optimally sensitive to vibrations at approximately 30 Hz. Vibrotactile prepulses with frequencies of 30 and 300 Hz and intensities of 95 and 130 mV were presented for 50 msec to the dominant hand of college students (N = 31), followed on some trials by a 95-dB broadband acoustic startle stimulus. The 300-Hz prepulses resulted in significantly more pronounced inhibition of startle magnitude, amplitude, and probability, whereas only the 30-Hz prepulses significantly facilitated blink latency. These results support the idea that the inhibition of acoustic startle is determined more by transient than by sustained aspects of vibrotactile prepulse stimuli. This study also demonstrates that different aspects of the startle response differentially reflect stimulus characteristics of the prepulse.     

Nitric oxide synthesis in the basolateral complex of the amygdala is required for the consolidation and expression of fear potentiated startle but not shock sensitization of the acoustic startle

Nitric oxide (NO) is synthesized as a result of N-methyl-d-asparate (NMDA) receptor activation, it acts as an retrograde neurotransmitter freely diffusing across cell membranes interacting with its targets in a non-synaptic manner. Consequently, NO has been described as an extension of NMDA receptor activation. The targets of NO include cellular components within the basolateral complex of the amygdala (BLA) that are necessary for the consolidation of conditioned fear as well as targets that can significantly modulate neurotransmission associated with its expression. Given that both are NMDA receptor associated processes, this implies that NO may be an important intermediary of NMDA receptor activation and both fear memory consolidation and expression. The current study sought to examine this using visual fear conditioning and fear potentiated startle. Three experiments were conducted, rats received intra-BLA microinfusions of the global nitric oxide synthase inhibitor l-NAME either prior to fear conditioning, or expression of learned fear. Furthermore, NO's ability to modulate a NMDA receptor independent fear process was assessed by microinfusing l-NAME into the BLA prior to examination of the shock sensitization of the acoustic startle affect. The results indicated that NO was, indeed, required for both the consolidation and expression of learned fear, whereas it was not required for NMDA independent shock enhanced startle responding. This study illustrates that NO plays a pivotal role in the examined NMDA associated fear processes.     

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.     

The fear potentiated startle effect

A differential conditioning study examined whether an acoustic startle probe, presented during extinction of an aversively conditioned visual stimulus, potentiated the reflex eyeblink response in humans and whether this potentiation varied with the change in affective valence of the conditioned stimulus. Sixty college students were randomly assigned to view a series of two slides, depicting either unpleasant/highly arousing, unpleasant/moderate arousing, neutral/calm, pleasant/moderate arousing or pleasant/highly arousing scenes and objects (duration: 8 sec). During preconditioning (8 trials) and extinction (24 trials) acoustic startle probes (white noise bursts [50 ms; 95 dBA] were administered during and between slide presentation). During acquisition (16 trials) CS+ was reinforced by an electric shock. Startle response magnitudes significantly increased from preconditioning to extinction and were substantially larger to CS+. Conditioned startle reflex augmentation linearly increased with the pleasantness of the slides. Furthermore, subjects showed a greater post-conditioning increase of judged aversiveness to slides that they had previously reported to be more pleasant, exactly paralleling the startle reflex results.

     

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.     

The startle response and auditory temporal summation in neonates

The present study assessed temporal summation of transient and sustained stimuli in the startle eyeblink response system in neonates during quiet sleep. Subjects received 100-dB(A), fast-rising broadband noise bursts of two types: (a) single stimuli varying in duration from 20 to 100 ms and (b) pairs of 3-ms bursts presented at interpulse intervals corresponding to the single-stimulus durations. In addition, a single 3-ms pulse was used as an anchor point for both stimulus types. For startle amplitude, single stimuli were more effective than were paired stimuli, but the temporal summation functions were similar for the two types of stimuli. Response amplitude increased as stimulus duration/interval increased to 50 ms, but not beyond. For startle probability, temporal summation was similar for single and paired stimuli at 20 ms. Pairs of pulses were equally effective at 20, 35, and 50 ms, beyond which the second pulse was not effective. Increasing the duration of single stimuli from 20 to 35 ms resulted in increased probability, illustrating a contribution of sustained summation beyond that of transient summation. Response latency was generally greater for paired than for single stimuli. The results suggest that temporal summation of brief stimuli is deficient in the neonate. These data were compared to adult data from an analogous study, and suggest that the transient system is immature in infants, and that this immaturity is expressed differently by startle amplitude, probability, and latency.     

Strategic and automatic threat processing in chronic musculoskeletal pain: a startle probe investigation

Attentional bias research with chronic pain samples has yielded conflicting results. In the present investigation the startle paradigm was used to test the postulate that fear-based mechanisms play an important role in attentional biases for pain-related threat in chronic pain. Participants, including 31 individuals with chronic musculoskeletal pain and 20 healthy controls, completed a startle task designed to measure attention to different types of words (neutral vs sensory pain vs affective pain vs health catastrophe) presented at different levels of cognitive processing (strategic vs automatic). Measures of fear-based individual difference variables, including anxiety sensitivity and fear of pain, were also completed. Startle amplitudes and latencies to acoustic startle probes that followed word presentations were recorded. Data were analyzed with repeated measures ANOVAs and correlational analysis. Significant between-group differences were found indicating that, relative to chronic pain participants, healthy controls had higher startle amplitude index scores for health catastrophe words. There was also a trend among patients with chronic pain for greater startle amplitude index scores for strategic presentations of sensory pain words. In the automatic condition, all participants demonstrated a lower startle latency index for sensory words relative to both affect and health catastrophe words, suggesting participants had more difficulty disengaging from affect and health catastrophe words or were more avoidant of sensory words. Correlational analyses indicated that startle response indices for words related to health catastrophe became more pronounced for chronic pain patients as anxiety sensitivity and fear of pain increased. Implications and directions for future research are discussed.     

Prepared movements are elicited early by startle

A startle stimulus has been shown to elicit a ballistic response in a reaction time (RT) task at very short latencies without involvement of the cerebral cortex (J. Valls-Sole, J. C. Rothwell, F. Gooulard, G. Cossu, & E. Munoz, 1999). The present authors examined the nature of the startle response. A simple RT task was used in which 8 participants performed arm extension movements to 3 target distances (20 degrees, 40 degrees, and 60 degrees ) in a blocked design. An unpredictable startling acoustic stimulus (124 dB) replaced the imperative stimulus in certain trials. The authors verified the presence of a startle response independent from the prepared response by observing electromyographic (EMG) activity in sternocleidomastoid and orbicularis oculi muscles. Findings indicated that when the participant was startled, the intended voluntary response was produced at significantly shorter response latencies. Furthermore, the kinematic variables of the observed response during startle trials for all 3 target distances were mostly unchanged. The EMG characteristics of the responses were not modified, indicating that the response produced was indeed the prepared and intended response.     

Acoustic startle threshold of the albino rat (Rattus norvegicus)

The startle threshold of the albino Sprague-Dawley rat runs parallel to the curve of the hearing threshold. The difference between the startle and hearing threshold is 87 dB (SPL) at a background noise level of 75 dB (SPL). At 110 dB (SPL), the threshold has a range from 2 kHz to 50 kHz with a minimum at 10 kHz and a second minimum at 40 kHz. Amplitude and latency of the startle response are not only dependent on the sensation level of the acoustic stimulus but also on the frequency. At threshold, only the head movement component of the startle response is elicited.     

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.     

The fear potentiated startle effect. Blink reflex modulation as a result of classical aversive conditioning

A differential conditioning study examined whether an acoustic startle probe, presented during extinction of an aversively conditioned visual stimulus, potentiated the reflex eyeblink response in humans and whether this potentiation varied with the change in affective valence of the conditioned stimulus. Sixty college students were randomly assigned to view a series of two slides, depicting either unpleasant/highly arousing, unpleasant/moderate arousing, neutral/calm, pleasant/moderate arousing or pleasant/highly arousing scenes and objects (duration: 8 sec). During preconditioning (8 trials) and extinction (24 trials) acoustic startle probes (white noise bursts [50 ms; 95 dBA] were administered during and between slide presentation). During acquisition (16 trials) CS+ was reinforced by an electric shock. Startle response magnitudes significantly increased from preconditioning to extinction and were substantially larger to CS+. Conditioned startle reflex augmentation linearly increased with the pleasantness of the slides. Furthermore, subjects showed a greater post-conditioning increase of judged aversiveness to slides that they had previously reported to be more pleasant, exactly paralleling the startle reflex results.