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PubMed1985

Cocaine: excitatory effects on sensorimotor reactivity measured with acoustic startle.

Cocaine (2.5-10 mg/kg) caused a dose-related increase in the amplitude of the acoustic startle reflex in rats. In contrast, procaine (5-40 mg/kg) caused a dose-related decrease in startle, indicating that the effects of cocaine could not be ascribed to its local anesthetic effects. Cocaine's excitatory effects were blocked by pretreatment with haloperidol (0.5 mg/kg) but not by cyproheptadine or prazosin. The excitatory effects of cocaine (10 mg/kg) were markedly attenuated by pretreatment with reserpine (5 mg/kg 24 and 18 h earlier) but not by alpha-methyl-p-tyrosine (100 mg/kg 1 h earlier). In contrast, comparably sized excitatory effects of d-amphetamine were blocked by alpha-methyl-p-tyrosine and greatly enhanced by pretreatment with reserpine. Neither pretreatment blocked excitatory effects of apomorphine on startle. The data indicate that cocaine increases startle by acting through reserpine-sensitive pools of dopamine and provide further support for the conclusion that acoustic startle is enhanced by activation of dopamine receptors.

Acoustic Stimulation↗

PubMed2002

Major and minor form of hereditary hyperekplexia.

Hyperekplexia is a hereditary neurological disorder characterized by excessive startle responses. Within the disorder two clinical forms can be distinguished. The major form is characterized by continuous generalized stiffness in the first year of life and an exaggerated startle reflex, accompanied by temporary generalized stiffness and falls, whereas in the minor form only excessive startle and hypnic jerks have been described. Mutations in the gene encoding the alpha-1 subunit of the glycine receptor (GLRA1) are responsible for the major form of hyperekplexia but no mutation was detected in patients with the minor form in the large Dutch pedigree originally described by Suhren and colleagues. Here we describe the genetic analysis of the GLRA1 gene of two English families in which both forms of hyperekplexia were present. Mutation analysis revealed no genetic defect in the GLRA1 gene in patients carrying either the minor or major forms. This is further evidence that the minor form of hyperekplexia is seldom due to a genetic defect in the GLRA1 gene.

Adolescent↗

PubMed2004

Kynurenate in the pontine reticular formation inhibits acoustic and trigeminal nucleus-evoked startle, but not vestibular nucleus-evoked startle.

The startle reflex is elicited by acoustic, trigeminal or vestibular stimulation, or by combinations of these stimuli. Acoustic startle is mediated largely by ibotenate-sensitive neurons in the ventrocaudal pontine reticular formation (PnC). In these studies we tested whether startle elicited by stimulation of different modalities is affected by infusion of the non-selective glutamate antagonist, kynurenate, into the PnC. In awake rats, startle responses evoked by either acoustic or spinal trigeminal nucleus stimulation were inhibited by kynurenate, but not saline, infusions, with the most effective placements nearest PnC. In chloral hydrate-anesthetized rats, kynurenate in the PnC reduced trigeminal nucleus-evoked hindlimb EMG responses, but not vestibular nucleus-evoked startle. Kynurenate in the vestibular nucleus had no effect on trigeminal nucleus-evoked startle. These results indicate that trigeminal nucleus stimulation evokes startle largely through glutamate receptors in the PnC, similarly to acoustic startle, but vestibular nucleus-evoked startle is mediated through other pathways, such as the vestibulospinal tract.

Animals↗

PubMedDate not supplied

Conditioned-reflex facilitation in young and older adults.

Young (18-30 years) and elderly (63-88 years) human subjects received 70 trials of single-cue classical eyeblink conditioning (paired group), or 70 explicitly unpaired presentations of the tone conditioned stimulus (CS) and airpuff unconditioned stimulus (unpaired group). Before and after conditioning, reflex-eliciting white noise and corneal airpuff stimuli were presented alone or paired with the CS to investigate the effects of conditioning on eyeblink reflex amplitude. The results showed increased conditioned responses in the paired group compared to the unpaired group for the young but not the elderly subjects. There was, however, evidence of conditioned facilitation of noise-elicited reflexes in both young and elderly subjects. These data indicate that conditioned facilitation of the startle reflex may be a sensitive indicator of classical conditioning processes in human subjects.

Acoustic Stimulation↗

PubMed2005

Anticipation of public speaking in virtual reality reveals a relationship between trait social anxiety and startle reactivity.

BACKGROUND: Startle reflex modification has become valuable to the study of fear and anxiety, but few studies have explored startle reactivity in socially threatening situations. METHODS: Healthy participants ranging in trait social anxiety entered virtual reality (VR) that simulates standing center-stage in front of an audience to anticipate giving a speech and count backward. We measured startle and autonomic reactivity during anticipation of both tasks inside VR after a single baseline recording outside VR. RESULTS: Trait social anxiety, but not general trait anxiety, was positively correlated with startle before entering VR and most clearly during speech anticipation inside VR. Speech anticipation inside VR also elicited stronger physiologic responses relative to anticipation of counting. CONCLUSIONS: Under social-evaluative threat, startle reactivity showed robust relationships with fear of negative evaluation, a central aspect of social anxiety and clinical social phobia. Context-specific startle modification may be an endophenotype for subtypes of pathological anxiety.

Adult↗

PubMed1998

Acoustic startle, prepulse inhibition, locomotion, and latent inhibition in the neuroleptic-responsive (NR) and neuroleptic-nonresponsive (NNR) lines of mice.

The acoustic startle reflex (ASR) is inhibited by low intensity acoustic stimuli (prepulse inhibition; PPI) delivered prior to the startle stimulus. PPI may reflect underlying sensorimotor processes involved in the filtering of exteroceptive stimuli for their cognitive or physiological relevance. Latent inhibition (LI) is a cognitive process in which pre-exposure to the conditioned stimulus (CS) produces pro-active interference with the acquisition of an associative learning task. LI is thought to reflect a selective attention mechanism that contributes to an organism's ability to adjust its behavior to changing contingencies of reinforcement. In the present series of experiments, the ASR, PPI at three prepulse intensities (56, 68, and 80 dB), locomotor activity, and LI using an active avoidance paradigm were assessed in mice bidirectionally selected from a heterogeneous stock for response (NR line) or nonresponse (NNR line) to neuroleptic-induced catalepsy. A randomly selected line was used as the control. Mice from the NNR line displayed weak startle responses and a complete absence of PPI. In contrast, the NR line displayed the largest ASR and the greatest PPI. The control line displayed ASRs and PPI values intermediate to the selected lines. Locomotor activity which is known to affect LI was lowest in the NR line but was similar in the NNR and control lines. In the LI paradigm, acquisition of the avoidance response was impaired in mice from the NR and control lines that were pre-exposed to the auditory CS (normal response). In contrast, the acquisition of the avoidance response in the NNR line was similar in CS pre-exposed and CS non-pre-exposed animals. Overall, the results demonstrate that some of the same genetic factors which regulate neuroleptic response also play a significant role in PPI and LI.

Acoustic Stimulation↗

PubMed2000

Acoustic startle and fear-potentiated startle in rats selectively bred for fast and slow kindling rates: relation to monoamine activity.

The acoustic startle response, prepulse inhibition, fear-potentiated startle and monoamine activity induced by either, a novel stimulus or a cue previously paired with foot-shock (fear-conditioning), were assessed in rats selectively bred for differences in amygdala excitability (Fast vs. Slow kindling epileptogenesis). Comorbid differences of anxiety, which were dependent both on the rats' behavioural style and the kind of stressor, also characterized these strains. In the present investigation, Slow rats exhibited a greater startle reflex to noise relative to Fast rats, suggesting differences in generalized anxiety, but similar rates of startle habituation and prepulse inhibition. The fear-potentiated startle, however, was greater in Fast rats. When movement of the rat was restricted in a new environment, presentation of a novel stimulus (light) increased norepinephrine, dopamine and/or serotonin activity in brain regions typically associated with stressors (e.g. locus coeruleus, paraventricular hypothalamic nucleus). Generally, these effects were more pronounced in Fast rats, and norepinephrine utilization in the central amygdala was particularly highlighted in response to a conditioned fear stimulus. Thus, while generalized anxiety appeared greater in Slow rats, behavioural and central neurochemical reactivity in response to novel stimuli and to fear-eliciting stimuli, was greater in Fast rats. Similarly, basal dopamine activity in the prefrontal cortex was greater in Fast rats, but dopamine utilization elicited by a novel stimulus was more pronounced in Slow rats. This suggested that relative to Slow rats, dopamine neurons in prefrontal cortex of Fast rats do not react normally to environmental stimuli, and this phenomenon could lead to disturbances of attention or impulsivity.

Acoustic Stimulation↗

PubMed1985

Cutaneous and auditory function in rats following methyl mercury poisoning.

Rats were given a total dose of 50 mg/kg (Exp. 1), 13.3 or 40 mg/kg (Exp. 2), or 40 mg/kg (Exp. 3) of methyl mercury chloride subcutaneously over a course of 5 days. At varying times after the toxic exposure, up to 1 year, their sensory functioning was assessed by reflex modulation methods: stimuli of interest were presented just before an intense tone which elicited the startle reflex, and stimulus reception was measured by the inhibitory control of the stimuli over the amplitude of the reflex. In Experiment 1 cutaneous prestimuli (electric shock to the tail) and brief acoustic transients (silent periods in noise) were less effective inhibitors of reflex activity in poisoned animals, compared to controls, indicating that the poisoned animals had impairments in cutaneous sensitivity and audition. In Experiment 2 the time course of sensory loss and subsequent recovery was studied. Impaired auditory function was shown further by a deficit in the effectiveness of weak noise pulses, and, in addition, the cutaneous deficit for weak tail shocks was accompanied by an exaggerated or hyperpathic response to more intense tail shocks. Experiment 3 confirmed the finding that the loss of sensitivity to weak shock was accompanied by an enhancement of the response to more intense shock. These data were related to peripheral neuropathy and shown to be analogous to certain clinical symptoms of Minamata disease reported in humans.

Acoustic Stimulation↗

PubMed1997

Anxiogenic effects of high illumination levels assessed with the acoustic startle response in rats.

Previous studies have shown that the amplitude of the acoustic startle reflex is increased by the presentation of aversive stimuli. In the present study, the amplitude of acoustic startle in rats was increased by exposure to high illumination levels. The effect was directly related to the intensity (0, 8, 70, and 700 footlamberts) of illumination (experiment I); was blocked by the anxiolytic compound buspirone (experiment II); and showed little or no habituation with repeated testing (experiment III). These results suggest that the elevation of startle amplitude by light may reflect an unconditioned anxiogenic effect of high illumination levels. The possible utility of this phenomenon as an animal model of anxiety is discussed.

Acoustic Stimulation↗

PubMed1997

Auditory startle responses in help-seeking trauma survivors.

Studies of the acoustic startle reflex in post-traumatic stress disorder (PTSD) yielded controversial results, whilst PTSD patients consistently report exaggerated startle. Addressing methodological difficulties of previous studies, the authors investigated the eyeblink, skin conductance and heart rate responses to 15 consecutive 95-dB, 500-ms, 1000-Hz sudden tones in 58 consecutive referrals of unmedicated help-seeking trauma survivors (30 with PTSD and 28 without PTSD). PTSD patients had higher average eyeblink and skin conductance responses to the tones. Differences between reports of exaggerated startle in PTSD and negative experimental findings may be explained by specific experimental conditions, such as reduced environmental input, and by concurrent use of medication.

Adult↗

PubMed1995

Orolaryngeal reflex responses to changes in affective state.

Previous research has shown that the eye-blink startle reflex can be modulated by changes in affective state. The purpose of the present study was to determine whether human perioral and trigemino-laryngeal reflexes are sensitive to affective state changes. Impetus for this study comes from theories suggesting that orolaryngeal reflexes may be modulated by affective states, and as such influence voice and speech production. Subjects were 24 classically trained female sopranos (21-35 years). Each produced a pursing lip posture while sustaining the continuant /m/ at 440 Hz and at a comfortable voice intensity level. Simultaneously subjects were shown an aversive, pleasant, or neutral slide (experimental conditions) or no slide (control condition) and received unanticipated, servo-controlled mechanical taps to the midline upper lip. Perioral responses were recorded bilaterally from the orbicularis oris inferior (OOI) muscle using surface electromyography (EMG). Trigemino-laryngeal responses were obtained indirectly by measuring changes in the voltage analog of the voice fundamental frequency (VF0). Reflex responses were detected by smoothing and signal-averaging the VF0 and rectified EMG signals. Response magnitude and latency measures were compared across the affective valence and no-slide conditions. Statistically significant differences were not observed between conditions for the magnitude or temporal measures of either reflex. Significant differences, independent of affective valence, were observed between right and left early excitatory perioral response magnitudes. Differences between the startle and orolaryngeal reflexes, as well as the implications of these findings for speech motor control, are discussed.

Adult↗

PubMed1991

The startle eyeblink response to low intensity acoustic stimuli.

Four experiments were conducted to investigate the acoustic startle response to stimuli of low intensities. Eyeblink responses (integrated EMG from orbicularis oculi) were measured from male and female college students. Experiment 1 compared tone and noise stimuli varying in intensity (50 and 60 dB(A) SPL), with noise stimuli producing greater response amplitude and probability than tone stimuli. Experiment 2 was designed to investigate temporal summation of low intensity stimuli using single and paired 70dB(A) SPL broadband noises, and an onset-to-onset interval between the brief stimuli in a pair equal to the duration of the single stimuli. Increasing the duration of single stimuli resulted in larger responses, illustrating temporal summation. Experiment 3 used 60 and 70 dB(A) SPL broadband noise varying in rise/fall time, with faster-rising stimuli producing larger responses, and more intense stimuli producing larger and more probable responding. Experiment 4 employed the startle modification paradigm using 60 and 70 dB(A) SPL broadband noises as startle stimuli and a 50dB(A) SPL tone as a prepulse. Response amplitude and probability to both 60 and 70 dB(A) SPL stimuli were significantly inhibited by the 50dB(A) SPL prepulse. These studies show that the acoustic startle response is more sensitive than previously thought, and the elicitation of startle by low intensity stimuli argues against the limitation of the startle reflex as a high intensity phenomenon. These findings can increase the application of this response system by showing that startle stimuli need not be of high intensity, because reliable and differential startle can be elicited and modified at relatively low stimulus intensities.

Adolescent↗

PubMed1994

Modulation of the acoustic startle response by film-induced fear and sexual arousal.

The response matching model of Lang, Bradley, and Cuthbert (1992) predicts startle reflex facilitation during negative relative to positive emotional states. Using slide and imagery paradigms, larger eyeblink responses to startle probes for unpleasant than for pleasant conditions have consistently been reported. The present study extended the previously observed relationship between valence and startle to more complex stimuli, namely 1-min film fragments. Thirty-three subjects viewed a sequence of 27 film fragments with neutral, negative (fearful), and positive (sexual) contents, presented in one of three mixed orders. Blink magnitude to brief bursts of white noise was larger during fearful fragments than during sexual fragments. Blink magnitudes habituated across successive film fragments, but the positive-negative difference remained stable within film fragments and during the entire length of the videotape (approximately 40 min).

Acoustic Stimulation↗

PubMedDate not supplied

Behavioral characteristics of mice with genetic knockout of monoamine oxidase type A.

Transgenic mice of line Tg8 were used to study the effects of deletion of the monoamine oxidase type A gene and the absence of the corresponding enzyme on behavior. These experiments showed that Tg8 mice with genetic knockout of monoamine oxidase type A differed from mice of the parental line C3H/HeJ by lower levels of the startle reflex in response to an acoustic signal, while there was no difference in the prestimulus inhibition of the startle response. Tg8 mice showed decreased investigative activity and decreases in the number of sector crossings in the light-dark anxiety test. There were significant increases in aggression as a motivation in male Tg8 mice, which was manifest as an increase in the number of mice demonstrating aggression and a decrease in the latent period of attack. The intensity of aggression changed to a lesser extent - the number of fights even decreased, though longer periods of keeping mice together resulted in increased numbers of deaths among intruder mice. At the same time, there were no significant differences between mice with genetic knockout of monoamine oxidase type A and control mice in terms of the expression of sexual activation: the behavioral responses of Tg8 males to presentation of females was marked and was no different from that of male C3H/HeJ mice. Knockout of the gene had no effect on movement activity on behavior in an elevated cross-shaped maze or in the test for predisposition to catalepsy.

Aggression↗

PubMed2001

Startle response during smoking and 24 h after withdrawal predicts successful smoking cessation.

RATIONALE: The startle response is thought to reflect changes in attentional processes in humans. The startle response shows a number of forms of plasticity, of which prepulse inhibition (PPI) refers to the attenuation of the startle response to a strong sensory stimulus (pulse), when such a pulse is preceded by a stimulus of lower intensity (prepulse). Recent studies have shown that nicotine modulates startle and PPI of the startle reflex in humans and animals. The present study examined individual differences in cognitive benefits obtained from smoking as indexed by startle response and PPI. OBJECTIVES: We investigated, using a within-subjects design, the effects of cigarette smoking via a comparison of baseline and withdrawal measures of startle and PPI in 18 subjects wishing to quit cigarette smoking. The relapse of five of these subjects enabled a between-group comparison of these measures with the successful quitters. METHODS: Startle and PPI were measured on three separate occasions: before quitting, 24 h after quitting and 1 month after quitting. RESULTS: The presence of a high startle response amplitude while subjects were still engaged in their normal smoking patterns (baseline) and the occurrence of a significant drop of startle amplitude in withdrawal relative to baseline factors were found to be predictive of an individual's ability to quit smoking. Changes in PPI were found to reflect these changes in startle amplitude. CONCLUSIONS: The observed response patterns are discussed in terms of individual differences in commitment to quitting and self-dosing to manipulate attentional mechanisms as measured by the acoustic startle response. Furthermore, it is suggested that these specific response profiles may be predictive of the ability to quit smoking.

Adult↗

PubMed1997

Infusion of quinpirole and muscimol into the ventral tegmental area inhibits fear-potentiated startle: implications for the role of dopamine in fear expression.

Dopamine (DA) D2 and gamma-aminobutyric acid (GABA)A somatodendritic receptors tonically inhibit mesolimbic projection neurons in the A10 DA cell grouping of the ventral tegmentum. In the present study we determined the contribution of the ventral tegmental area (VTA) to the expression of a classically conditioned fear-induced increase in the acoustic startle reflex. Saline applied to VTA neurons did not modify the capacity of a light previously associated with footshock to potentiate acoustic startle amplitudes; conversely, bilateral administration of the DA D2/3 agonist quinpirole or the GABAA receptor agonist muscimol into the ventral tegmentum blocked fear-potentiated startle without altering baseline acoustic startle responding. It was suggested that DA VTA neurons regulate the excitatory aspects of fear expression by gating levels of aversive emotional arousal within the amygdala-based fear system.

Analysis of Variance↗

PubMed1984

Diethyldithiocarbamate depresses the acoustic startle response in rats.

The relationship between norepinephrine (NE) content in cortex and spinal cord and acoustic startle amplitude was investigated in two experiments. Administration of diethyldithiocarbamate (DDC) depressed startle amplitude at the same time and dose that it most severely depleted NE content. These results support the conclusion that NE facilitates the normal elaboration of the acoustic startle reflex and also support evidence that NE activity in the spinal cord may be of particular importance in the maintenance of normal startle amplitude.

Acoustic Stimulation↗

PubMed2001

Growth and development in rats given recombinant human epidermal growth factor(1-48) as neonates.

To assess effects of supraphysiologic doses of human recombinant epidermal growth factor(1-48) (rhEGF(1-48)) on neonatal rats, 10 litters of Wistar rats/treatment group were given 0 (formulated vehicle), 10, 100, or 1000 microg/kg daily by subcutaneous injection on postnatal days (PND) 1 through 6. Clinical signs, body weight, acquisition of developmental landmarks and reflexes, and behavior were monitored during treatment and for 5 weeks thereafter (to PND 42). A subset of animals was euthanized weekly from PND 7-28 and necropsied. Selected tissues were examined microscopically. Body weight gain at 1000 microg/kg during treatment was significantly less than control. Precocious incisor eruption, eye opening, vaginal opening, and preputial separation occurred at 100 and/or 1000 microg/kg. Acquisition of reflexes (negative geotaxis, wire maneuver, acoustic startle reflex, and visual placing) was delayed at 1000 microg/kg. Acquisition of adult locomotion was also delayed at 1000 microg/kg. These effects were transient, as locomotor activity at PND 28 and 42 did not differ from control. Effects on acoustic-startle responding persisted in females to final assessment on PND 42. Habituation to repeated acoustic stimuli was impaired, as well as response inhibition following a prepulse acoustic stimulus. rhEGF(1-48) induced structural changes in the skin, retina, kidney, oral and nasal mucosa, lung, and liver. Many of these changes were consistent with the expected mitogenic activity of rhEGF(1-48) and were transient in nature, as severity and incidence diminished with time. An exception was changes observed in the retina at 1000 microg/kg (rosettes/folds and focal defects in the outer nuclear/photoreceptor layers) that were still present 3 weeks after termination of treatment. Acceleration of developmental landmarks; suppression of reflexes, behavior, and somatic growth; and mitogenic responses in epidermal tissues have been reported in rodents treated with epidermal growth factor (EGF) derived from various mammalian species. These results demonstrate that a 48-amino acid fragment of human EGF produced by recombinant technology also induces such effects.

Acoustic Stimulation↗