Effects of inferior colliculus lesions on the acoustic startle response.

"Nonspecific" electrolytic lesions (with respect to subdivision) of the mouse inferior colliculus (IC) resulted in the attenuation of acoustic startle response (ASR) amplitudes of the 1st postoperative day, but ASR amplitudes increased to above baseline levels 1 wk later. Lesions of the IC central nucleus (CN) also attenuated ASR amplitudes on the 1st postsurgery day, but startle amplitudes recovered to baseline levels 1 wk after surgery. Lesions of the IC lateral nucleus (LN) or dorsal cortex (DC) resulted in elevation of startle amplitudes above baseline 7 days after surgery and produced enhanced ASR amplitudes to repeated stimuli. 14 days after the surgery, lesion effects on startle amplitudes remained the same as those on Day 7 for each lesion condition. The present findings implicate the ICLN and ICDC as inhibitory modulators of the ASR, but indicate only a minor role for the ICCN. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Olfactory-mediated fear-potentiated startle.

Recently, R. Richardson, A. Vishney, and J. Lee (1999) reported that ambient odor cues that were previously paired with footshock potentiate the acoustic startle response in rats. The authors of the present study extend those findings by using a discrete 4-s amyl acetate odor paired with footshock to address several parametric issues that might be important for using odorants as conditioned stimuli (CSs) in this paradigm. Amyl acetate (5%) had no significant effect on startle in untrained rats but did potentiate startle in rats that received 1, 2, 5, or 10 odor-shock pairings. Fear-potentiated startle decreased but was still significant up to 40 days after conditioning and could be measured in test trials separated by as little as 30 s. The magnitude of potentiated startle decreased with decreasing concentrations of amyl acetate (5%-5 x 10-9%). The anxiolytic compound buspirone (10 mg/kg) significantly attenuated olfactory-mediated fear-potentiated startle. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rearing experience differentially affects somatic and cardiac startle responses in rhesus monkeys (Macaca mulatta).

The present study reports, for the first time, somatic and cardiac responses to acoustic startle in 2 groups of rhesus monkeys (Macaca mulatta) with different rearing experiences. Both groups showed a significant direct relationship between startle amplitude and the intensity of the acoustic startle stimulus (80-120 dB) and rapid heart rate acceleration after a 120-dB stimulus. Monkeys reared with a same-age peer (PR) showed higher startle amplitudes than those reared with their mothers (MR), consistent with rearing effects in rodents. The MR monkeys, however, showed faster heart rate acceleration of greater overall magnitude than that of the PR group. The results are discussed with regard to a monkey model for neuropsychiatric disease. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fear-potentiated startle in two strains of inbred mice.

The fear-potentiated startle paradigm has been used with great success to examine conditioned fear in both rats and humans. The purpose of this study was to examine fear-potentiated startle in inbred mice. One-month-old C57BL/6J (C57) and DBA/2J (DBA) mice were given tone?+?foot shock training trials. The amplitude of the acoustic startle reflex was measured in the presence and absence of the tone both before and after training. Both strains showed fear-potentiated startle after training as evidenced by larger startle amplitudes in the presence of the tone than in its absence. However, the magnitude of fear-potentiated startle was greater in DBA mice than in C57 mice. These results not only demonstrate fear-potentiated startle in mice for the first time but also suggest that fear-potentiated startle can be influenced by characteristics of the mouse strain. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Affective reactivity of language symptoms, startle responding, and inhibition in schizophrenia.

The speech of some schizophrenia patients becomes markedly more disordered when negative affect is aroused. The authors tested associations between affective reactivity of speech and responsiveness and inhibition on an acoustic startle task in a sample of 27 outpatients. Patients whose language was reactive to negative affect showed significantly higher initial startle amplitudes than those whose language was not reactive. However, they also showed greater habituation to repeated startle stimuli over trials, even after differences in initial amplitudes were controlled statistically. These findings suggest that affective reactivity of speech is associated with higher initial startle responsiveness but also with greater habituation and, conversely, that patients who are relatively nonreactive to excitatory affective and sensory stimuli are also less reactive to inhibitory input. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Circadian modulation in the rat acoustic startle circuit.

The acoustic startle reflex (ASR) in rats exhibits robust circadian modulation, with ASR amplitudes greater during subjective night. To identify the location of this modulation, startle reactions were evoked either acoustically or electrically via electrodes implanted in the primary ASR circuit. Startle amplitudes were compared at different times in the circadian cycle. In constant environmental conditions, startle amplitudes were greater in subjective night for acoustically evolved and for electrically evoked reactions from the ventral lateral lemniscus and medial longitudinal fasciculus. The results show that at least 1 site of circadian modulation must occur at some point in the circuit after the last brainstem synapse in the caudal pontine reticular formation, at the level of spinal interneurons or motoneurons or at the neuromuscular junction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Orbital decompression in exophthalmos due to thyroid disease. Report of 69 cases]

Preclinical studies suggest that acoustic startle amplitude is increased during ethanol withdrawal. The current study evaluated the effects of intravenous infusion of the alpha 2-adrenergic antagonist, yohimbine (0.4 mg/kg), the serotonin partial agonist m-chlorophenylpiperazine (mCPP, 0.1 mg/kg), and placebo administered to 22 male patients meeting DSM-III-R criteria for alcohol dependence and 13 male healthy subjects. Patients and healthy subjects completed 3 test days under double-blind conditions in a randomized order. Patients were sober for 12-26 days prior to testing. On each test day, participants completed startle testing 80 min following drug infusion. Stimuli with varying intensities (90, 96, 102, 108, 114 dB) were presented in a randomized order balanced across four blocks. Stimuli consisted of 40-ms bursts of white noise administered every 45-60 s for 15-20 min through headphones. Analyses indicated that patients exhibited elevated acoustic startle magnitudes on the placebo day relative to healthy subjects. In patients, the magnitude of startle amplitudes elicited at 90 dB, but not 114 dB, correlated significantly with the number of previous alcohol detoxifications. Yohimbine increased startle magnitudes and reduced startle latencies relative to placebo and mCPP in both patients and healthy subjects. mCPP did not alter startle magnitude in either group. Yohimbine also increased the probability that a 90-dB stimulus produced a startle response in healthy subjects, but not in patients. Blunting of yohimbine effects on startle probability may reflect the baseline elevations in startle probability levels in patients, but may also be consistent with other evidence of reduced postsynaptic, but not presynaptic, noradrenergic function in these same patients. These data replicate and extend previous reports indicating that yohimbine facilitates the acoustic startle response in humans. They also further implicate the number of episodes of ethanol withdrawal as a factor influencing subsequent neurobiological responsivity in chronic alcoholic patients. Based on the current data, future research should explore whether measurement of the acoustic startle response provides an objective quantitative severity measure of ethanol withdrawal.     

Intra-amygdala infusion of the N-methyl-D-aspartate receptor antagonist AP5 blocks acquisition but not expression of fear-potentiated startle to an auditory conditioned stimulus.

The fear-potentiated startle paradigm, in which the amplitude of the startle reflex is enhanced in the presence of a stimulus previously paired with footshock, was used to measure aversive conditioning after intra-amygdala infusion of the competitive N-methyl-{d}-aspartate (NMDA) receptor antagonist {dl}-2-amino-5-phosphonopentanoic acid (AP5). Infusion of 2.5 μg/side AP5 immediately before 5 noise–footshock pairings on each of 2 consecutive days dose-dependently blocked acquisition or consolidation of auditory fear-potentiated startle, consistent with previous results obtained with a visual stimulus. Somatosensory or auditory transmission deficits do not appear to be induced by intra-amygdala AP5, because rats reacted normally to footshocks and showed reliable potentiated startle expression after pretesting AP5 infusion at a dose that blocked acquisition. Together with earlier reports, these data suggest that an NMDA-dependent process localized in or near the amygdala may be necessary for the acquisition of conditioned fear across different sensory modalities. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Potentiated startle: Its relation to freezing and shock intensity in rats.

Two experiments with 47 albino rats measured acoustic startle response and freezing in a potentiated startle paradigm in which a startle stimulus was presented either alone or in the presence of a light conditioned stimulus/stimuli (CS) that had been paired previously with either 1-mA or 3-mA footshock. During the CS, the 1-mA group had higher startle amplitudes and a higher percentage of freezing than the 3-mA group. Startle amplitude was positively correlated with freezing under all conditions. The nonmonotonic relation between potentiated startle and shock intensity replicated the study of M. Davis and D. I. Astrachan (see record 1979-00353-001). However, rather than suppressing startle, as they suggested, freezing facilitated startle and, like startle amplitude, was nonmonotonically related to shock intensity. In Exp II, these results were replicated and showed a regularly decreasing monotonic extinction function or potentiated startle and shock-associated freezing for both shock-level groups. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contribution of ventral tegmental area dopamine neurons to expression of conditional fear: Effects of electrical stimulation, excitotoxin lesions, and quinpirole infusion on potentiated startle in rats.

Potentiated startle was used in this study to determine the fear-motivational functions of the ventral tegmental area (VTA) in rats. In Experiment 1, electrical stimulation of the VTA increased acoustic startle amplitudes. In subsequent experiments fear-potentiated startle was assessed following axon-sparing N-methyl-D-aspartate (NMDA) lesions of the VTA and after bilateral intra-VTA infusion of the dopamine (DA) D2/3 receptor agonist quinpirole. The NMDA lesions produced substantial cell loss in the medial ventral tegmentum and suppressed fear expression. Similarly, inhibition of DA neuronal activity associated with locally administered quinpirole blocked fear-potentiated startle. It was suggested that VTA neurons and their forebrain DA projections regulate levels of aversive emotional arousal within the amygdala-based fear system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acoustic startle response and habituation in freezing and nonfreezing rats.

Divided rats according to their responses to startle-eliciting stimuli into 2 groups with different emotional states. About half of the 54 female Sprague-Dawley rats showed long-lasting freezing behavior after 1–8 stimuli (10 kHz, 110 dB spl). In freezing rats the startle amplitude was higher than in nonfreezing rats, even on the very first startle response. This finding demonstrates that the anxiety state of these animals before the 1st startle-eliciting stimulus, and not just the aversiveness of the stimulus, contributes to freezing behavior. In addition, in freezing rats there was no influence of spontaneous motor activity or of adaptation time on startle amplitude. Only in nonfreezing rats were high motor activities correlated with lowered startle amplitudes, and only in these rats did the course of startle habituation depend on adaptation time. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

High Illumination Levels Potentiate the Acoustic Startle Response in Preweanling Rats.

Fear potentiation of the acoustic startle response (FPS) by aversive conditioned stimuli does not emerge in rats until Postnatal Day (P)23 (see P. S. Hunt & B. A. Campbell, 1997). However, the present study found that when presented with an unconditioned fear-eliciting stimulus, rats younger than P23 display FPS. Specifically, high illumination levels were found to enhance startle amplitudes in rats aged 18 and 25 days, but not 14 days. Furthermore, the light-enhanced startle observed in P18 rats was prevented by a systemic injection of the noradrenergic beta-receptor antagonist propranolol. These data suggest that conditioned and unconditioned FPS have different ontogenetic trajectories, and thereby provide support for the idea that learned and unlearned fear are subserved by dissociable neural systems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The CCKB antagonist, L-365,260, attenuates fear-potentiated startle

The neuropeptide cholecystokinin (CCK), via the CCKB receptor, increases behaviors associated with anxiety in laboratory animals and humans. The present experiment assessed the role of endogenous CCKB function in fear-potentiated startle, a test of "anxiety" in rats. The amplitude of the acoustic startle response is potentiated if preceded by a stimulus that has been previously paired with shock. Pretreatment with the CCKB antagonist L-365,260 (0, 0.1, 1.0, and 10.0 mg/kg, IP) did not affect baseline acoustic startle amplitudes, but dose-dependently decreased fear-potentiated startle. These results indicate that the specific attenuation of fear-potentiated startle induced by L-365,260 was not due to a general decrease in motor responsivity. The present findings are consistent with the effects of CCKB antagonists in other tests measuring anxiety in animals.     

Involvement of NMDA receptors within the amygdala in short- versus long-term memory for fear conditioning as assessed with fear-potentiated startle.

Pretraining intra-amygdala infusions of the NMDA receptor antagonist, D,L-AP5, block fear-potentiated startle in rats tested 24+ hr after training. This may reflect a failure of either acquisition or retention. To evaluate these alternatives, rats were tested for fear-potentiated startle during fear conditioning (30 light-shock pairings [0.6 mA shock]), as well as 1–30 min and 48 hr after fear conditioning. Amygdala lesions abolishes fear-potentiated startle at all train-test intervals. Intra-amygdala AP5 infusions (25 nmol/side) abolished fear-potentiated startle during the long-term test and had partial effects at shorter train-test intervals. When the level of fear-potentiated startle during the short-term test was lowered to that of the 48-hr test (i.e., by training rats with a lower, 0.3 mA footshock), AP5 abolished fear-potentiated startle at each timepoint. Thus, amygdala NMDA receptors appear to participate in the initial acquisition of fear memories. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Event-related potentials during an auditory discrimination with prepulse inhibition in patients with schizophrenia, obsessive-compulsive disorder and healthy subjects

Prepulse inhibition (PPI) is a measure of the influence of a stimulus (S1) on the response elicited by a second stimulus (S2) occurring shortly afterwards. Most S1/S2 measures of gating have used behavioural startle and the P50 event-related potential (ERP) amplitudes to detect PPI in a simple paired stimulus paradigm. We report on two behavioural (reaction time, RT, and the electromyographically recorded response of the musculus orbicularis oculi, EMG) and 5 ERP measures of PPI where S2 was the target in an auditory two-tone discrimination. Subjects were 21 healthy controls (CON), 11 obsessive-compulsive (OCD) and 9 schizophrenic patients (SCH). The prepulse 100 ms before S2 induced more omission errors and longer RTs compared to 500ms S1-S2 interval in all subjects. PPI was also evident in EMG, P50, N1, P3 but not P2 or N2 amplitudes of CON subjects. SCH patients showed attenuation of PPI on the same measures. OCD patients were characterized only by their slow RT and a marginal attenuation of PPI of the EMG response. A correlational analysis implied separate relationships of ERP indices of PPI to the cognitive and psychomotor consequences of the prepulse on behavioural and discrimination responses. However, SCH patients showed a general rather than a specific impairment of these indices.     

Fear-potentiated startle and electrically evoked startle mediated by synapses in rostrolateral midbrain.

Startle amplitudes are increased when acoustic startle responses are elicited in the presence of a stimulus that has previously been paired with shock. This "fear-potentiated" startle response appears to be mediated via the caudal ventral amygdalofugal pathway to the brainstem. Electrical stimulation of this pathway evokes unconditioned startlelike responses. Collision tests have shown that a monosynaptic connection from amygdala to midbrain mediates these responses. Collision tests here localize these synapses mediating electrically evoked startlelike responses to the rostrolateral midbrain in awake rats. To test whether rostrolateral midbrain synapses also mediate fear-potentiated startle, we lesioned cells in these sites with ibotenic acid. These lesions completely blocked fear potentiation of acoustic startle. These same lesions did not block potentiation of startle by d-amphetamine (6 mg/kg). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cocaine enhances the expression of fear-potentiated startle: Evaluation of state-dependent extinction and the shock-sensitization of acoustic startle.

Cocaine's effects on fear extinction and on the shock-sensitization of acoustic startle were examined. Following fear acquisition, rats exposed to the nonreinforced CS after cocaine administration demonstrated significant levels of fear-potentiated startle when evaluated in the drug-free state. The CS also increased startle amplitudes in subjects extinguished and tested with cocaine, indicating that mechanisms other than state-dependent learning are involved in the extinction deficit. The presentation of 10 footshocks augmented acoustic startle, and the shock enhancement was unaffected by cocaine preexposure. These data indicate that the aversive consequences of footshock relevant to the acquisition of conditional fear are not sensitized by the drug. It was suggested that cocaine reinforces fear responding to a threatening stimulus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acoustic startle response in young and aging C57BL/6J and CBA/J mice.

C57 mice demonstrate progressive age-related hearing loss during the 1st yr, whereas CBA mice lose little sensitivity through 18 mo of age. The acoustic startle response (ASR) was measured to determine behavioral correlates of aging with and without presbycusis. Stimuli were tone pips with frequencies of 4–24 kHz at intensities of 70–200 dB SPL. ASR thresholds increased with age, and startle amplitudes became smaller. Changes in startle parameters were more pronounced in C57 mice, with middle to high frequencies severely affected. Startle latencies at and above ASR threshold increased with age in C57 mice. CBA data indicate that aging has little effect on ASR parameters; the C57 data show that hearing loss is a cogent factor. ASR parameters of C57 mice are altered to a greater extent than expected, on the basis of the elevations of absolute sensory thresholds, particularly for middle frequencies. Both peripheral and central mechanisms may account for the discrepancy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)