Acoustic Startle Habituation Research Articles

The Effects of Caffeine and Directed Attention on Acoustic Startle Habituation

The present experiment tested the effects of caffeine on acoustic startle habituation during different attention tasks in which subjects either (a) attended to the acoustic startle stimulus (auditory attention; n = 9) (b) attended to a visual search task during presentation of acoustic startle stimuli (visual attention; n = 10), or (c) were given no specific instructions during acoustic startle testing (no attention; n = 9). Startle eyeblink responses were measured after subjects received either caffeine (1 mg/kg) or placebo. Caffeine significantly delayed response habituation in the no attention group and in the auditory attention group, but had no effect on habituation in the visual attention group. These data show that startle habituation can occur with minimal attention being directed to the acoustic startle stimulus, and that visual attention cancels the effects of caffeine on startle habituation.

The effects of different doses of caffeine on habituation of the human acoustic startle reflex

Research in this laboratory showed that caffeine (4 mg/kg) delays habituation of the acoustic startle reflex in humans. The present study examined the effects of 2- and 6-mg/kg doses of caffeine on acoustic startle habituation in moderate-high and low caffeine users. Eyeblink responses to 30 trials of 85-dB noise stimuli were measured beginning 30 min after oral ingestion of either placebo or 2 or 6 mg/kg of caffeine. The 2-mg/kg dose of caffeine delayed startle habituation in both moderate-high and low caffeine users. The 6-mg/kg dose produced no differential effects on startle responding from placebo. In moderate-high users, following habituation, startle responding was smaller in the placebo condition compared to both caffeine conditions. In low users there were no differences in posthabituation responding between doses, suggesting that this dose effect is dependent on a history of chronic caffeine usage.

Nicotine modulates effects of stress on acoustic startle reflexes in rats: dependence on dose, stressor and initial reactivity

Cigarette smokers report that one reason for smoking is that smoking helps them cope with stress, but there is conflicting evidence as to whether nicotine reduces physiological and behavioral responses to stress. The acoustic startle reflex amplitude, pre-pulse inhibition, and habituation of the reflex provide quantifiable measures of behavioral reactivity that may be sensitive to stress-induced changes that are altered by nicotine. In the present experiment, rats classified as high and low reactors according to baseline startle amplitudes were administered nicotine (6 or 12 mg/kg/day) or saline by osmotic minipump for 11 days. On day 11, animals were acutely stressed by restraint or observation of restraint of conspecifics prior to startle measurement. Nicotine and stress each independently increased acoustic startle amplitude and amount of pre-pulse inhibition, but in combination, the effect of restraint stress and 12 mg/kg nicotine were indistinguishable from saline-treated, non-stressed controls. In contrast, the 6 mg/kg nicotine dose enhanced effects of both restraint and observation stressors on startle amplitude and pre-pulse inhibition. Animals classified as highly reactive prior to treatment were more responsive to nicotine, stress, and the combination, suggesting that initial reactivity is an important determinant of drug and stress effects. Results indicate that nicotine can both reduce and enhance stress effects on reflex amplitude and pre-pulse inhibition depending upon nicotine dose, stressor, and individual differences in reactivity.

Habituation of acoustic startle in rats--a functional ablation study.

Data from lesion studies data indicate that the removal of the medial cerebellum prevents acquisition but not retention of long-term habituation (LTH) of the acoustic startle response (ASR). The spreading depression (SD) of the vermis was used to examine under more functional conditions the build-up of LTH of the ASR in Wistar rats. Our findings showed that reversible blockade of the vermis during training disrupted LTH of the ASR without changing within-trials habituation. In contrast to previous data, the present results suggest that SD strongly affects the amplitude of the startle response. The data are discussed in respect to a role of the vermis in the control of emotional behaviour in animals.

Neurotoxicity Evaluation of N,N-Diethyl-m-toluamide (DEET) in Rats

Neurotoxicity Evaluation of N,N-Diethyl-m-toluamide (DEET) in Rats. Schoenig, G. P., Hartnagel, G. E., Jr., Schardein, J. L., and Vorhees, C. V. (1993). Fundam. Appl. Toxicol. 21, 355-365.The neurotoxic potential of N,N-diethyl-m-toluamide (DEET) was evaluated following acute oral administration or following multigeneration plus chronic dietary administration to the rat. For the acute study, rats were administered undiluted DEET at dose levels of 50, 200, or 500 mg/kg by gavage. A dose level of 500 mg/kg was considered to be the highest practical dose that could be evaluated in this study based upon observations of overt toxicity at 500 mg/kg and mortality at 1000 mg/kg in a dose range-finding study. The two measures of neurotoxicity evaluated in the acute study were functional observational battery (FOB) and motor activity measurements. An apparent treatment-related effect in thermal response time (increased) was noted for both sexes 1 hr after dosing at the 500 mg/kg dose level. A questionable effect on rearing activity (decreased) also was noted at the same dose level. For the multigeneration plus chronic dietary administration study, rats were administered DEET at dietary concentrations of 0, 500, 2000, or 5000 ppm continuously over two generations and then chronically for 9 months. A dietary concentration of 5000 ppm meets the criteria for a maximum tolerated dose (MTD) based on traditional chronic toxicology assessments. Evaluations included FOB, motor activity, discriminative acquisition and reversal in an M-maze, acoustic startle habituation, passive avoidance acquisition and retention, and microscopic examination of central and peripheral nervous tissue. The only effect that was considered to be possibly treatment-related was a slight increase in exploratory locomotor activity at the 5000 ppm dose level. Based on the results of these studies, the nervous system does not appear to be a selective target when DEET is administered to rats either as a single oral dose at high dose levels or chronically at the MTD.

Concurrent assessment of acoustic startle and auditory P50 evoked potential measures of sensory inhibition

The acoustic startle response (ASR) and midlatency auditory evoked potentials (AEP) have been utilized in the measurement of sensory inhibition. Using these different paradigms, abnormalities suggesting a lack of normal inhibition have been noted in a number of psychiatric syndromes. To date, the most commonly used sensory inhibition paradigms have not been studied in the same individuals, making generalizations across studies tenuous. In this report, reduction of ASR over multiple trials (habituation), prepulse inhibition (PPI) of ASR (decrease in ASR caused by low intensity prepulses) and P50 suppression (P50 AEP amplitude reduction in a paired-click paradigm) were measured in the same individuals. Relationships between these measures of acoustic startle and AEP inhibition were then assessed. Twenty subjects with no personal history of psychiatric disorder were tested and exhibited significant habituation and PPI of ASR as well as P50 suppression. Habituation of ASR was significantly and positively correlated with P50 suppression early, but not late, in AEP testing. Only a modest trend for a positive association between PPI and P50 suppression was noted. Habituation and PPI of startle were both highly correlated (positively) with P50 AEP amplitude. Habituation of startle remained significantly predictive of P50 suppression after controlling for P50 amplitude, whereas the modest association between PPI and P50 suppression was removed when P50 amplitude was factored out. Results indicate that habituation of acoustic startle, but not PPI, is highly associated with P50 suppression in control subjects. An unexpected finding was a robust positive correlation between P50 amplitude and both measures of startle inhibition. These findings and methodologic issues are discussed in terms of possible neural substrates involved in differrent measures of sensory inhibition.

Neurotoxicity Evaluation of N,N-Diethyl-m-toluamide (DEET) in Rats

The neurotoxic potential of N,N-diethyl-m-toluamide (DEET) was evaluated following acute oral administration or following multigeneration plus chronic dietary administration to the rat. For the acute study, rats were administered undiluted DEET at dose levels of 50, 200, or 500 mg/kg by gavage. A dose level of 500 mg/kg was considered to be the highest practical dose that could be evaluated in this study based upon observations of overt toxicity at 500 mg/kg and mortality at 1000 mg/ kg in a dose range-finding study. The two measures of neurotoxicity evaluated in the acute study were functional observational battery (FOB) and motor activity measurements. An apparent treatment-related effect in thermal response time (increased) was noted for both sexes 1 hr after dosing at the 500 mg/kg dose level. A questionable effect on rearing activity (decreased) also was noted at the same dose level. For the multigeneration plus chronic dietary administration study, rats were administered DEET at dietary concentrations of 0, 500, 2000, or 5000 ppm continuously over two generations and then chronically for 9 months. A dietary concentration of 5000 ppm meets the criteria for a maximum tolerated dose (MTD) based on traditional chronic toxicology assessments. Evaluations included FOB, motor activity, discriminative acquisition and reversal in an Mmaze, acoustic startle habituation, passive avoidance acquisition and retention, and microscopic examination of central and peripheral nervous tissue. The only effect that was considered to be possibly treatment-related was a slight increase in exploratory locomotor activity at the 5000 ppm dose level. Based on the results of these studies, the nervous system does not appear to be a selective target when DEET is administered to rats either as a single oral dose at high dose levels or chronically at the MTD.

Acoustic startle response and habituation in freezing and nonfreezing rats.

Acoustic startle response and habituation in freezing and nonfreezing rats.

Acoustic startle response and habituation in freezing and nonfreezing rats.

Rats can be divided 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 first 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.

Gating and habituation of the startle reflex in schizophrenic patients.

Schizophrenic patients exhibit impairments in both sensorimotor gating and habituation in a number of paradigms. Through human and animal model research, these fundamental cognitive deficits have well-described neurobiologic bases and offer insights into the neuroanatomic and neurotransmitter abnormalities that characterize patients with schizophrenic spectrum disorders. In this context, the startle response is particularly interesting, because it is a cross-species response to strong stimuli that is plastic or alterable using experimental and neurobiologic manipulations. Thirty-nine medicated schizophrenic patients and 37 normal control subjects were studied in a new electromyography based startle response paradigm in which both prepulse inhibition (an operational measure of sensorimotor gating) and habituation (the normal decrease in response magnitude to repeated stimuli over time) can be separated and assessed in one test session. The results indicate that schizophrenic patients have extensive deficits in both intramodal and cross-modal sensorimotor gating and a trend to show acoustic startle habituation deficits. The deficit in prepulse inhibition of startle amplitude exhibited by schizophrenic patients was evident when an acoustic prepulse stimulus preceded either an acoustic or a tactile startle stimulus. No deficit was observed in the prepulse-induced facilitation of startle latencies, indicating that the failure of gating was not due to a failure of stimulus detection. These findings suggest centrally mediated deficits in sensorimotor gating in schizophrenic patients.

Peripheral and central components of alerting: Habituation of acoustic startle, orienting responses, and elicited waveforms.

Behavioral orienting (OR), the acoustic startle reflex (ASR), pontogeniculooccipital (PGO) waves in the lateral geniculate body, and midlatency auditory evoked responses (MLR) represent components of alerting. The habituation rate for each was examined to test the hypothesis that OR, ASR, and PGO waves have related underlying neural mechanisms and determine the similarity in responsiveness between elicited PGO waves (PGOE) and elicited waves in the thalamic central lateral nucleus (CLE), a site that yields MLR. PGOE and CLE waves did not habituate in amplitude after 120 tones; however, the pattern of responses for each waveform was different. OR and ASR significantly decreased amplitude across trials with OR exhibiting a faster, more pronounced decrement. Some separation exists between the peripheral (OR and ASR) and central (PGOE and CLE) components of alerting. PGO and CL waves may have common underlying neural mechanisms.

Peripheral and central components of alerting: Habituation of acoustic startle, orienting responses, and elicited waveforms.

Peripheral and central components of alerting: Habituation of acoustic startle, orienting responses, and elicited waveforms.

Effects of systemic and intra-amygdaloid diazepam on long-term habituation of acoustic startle in rats

Two experiments were conducted to examine the effects of the anxiolytic drug, diazepam, on long-term habituation of the acoustic startle response. The experiments were based upon the hypothesis that manipulations that reduce fear should enhance long-term response decrements by reducing a fear-like sensitization process. In Experiment 1 rats given intraperitoneal injections of 0.5, 1.2, or 2.5 mg/kg showed larger decrements of startle amplitude than vehicle-injected controls both over trials within sessions and over days. In Experiment 2 rats injected with 35 micrograms of diazepam bilaterally into the amygdala showed larger decrements of startle amplitudes over days than vehicle-injected controls. No within-session startle effects were detected in Experiment 2. Freezing behavior was measured in Experiment 2 as an index of fear, and the amygdala injections of diazepam retarded the development of fear in the startle chamber. This index of fear was not possible in Experiment 1 because of the sedating effects of systemic diazepam. We conclude that diazepam, acting at least in part through the amygdala, attenuates the fear-like sensitization process associated with the acoustic startle stimulus. By attenuating sensitization diazepam produces larger than normal reductions in startle amplitudes over trials and days without significantly affecting initial responsiveness.

Structural modeling of functional neural pathways mapped with 2-deoxyglucose: effects of acoustic startle habituation on the auditory system

This paper describes the first application of structural modeling to neuroscience. Structural modeling (also known as path analysis) is a method to assess the relative impact of directional links in a system and how these interrelations may change under different conditions. The objective was to demonstrate how structural modeling can be used to determine the functional interrelationships between brain structures that form the auditory system. Using structural modeling, changes in auditory system 2-DG uptake were examined during long- and short-term habituation of the acoustic startle reflex. Models were based on the anatomical connections between central auditory system structures. Using functional 2-DG data, the correlations between these structures were calculated and numerical weights were computed for each anatomical link. The analysis revealed that the lemniscal path was dominant during short-term habituation, while during long-term habituation this influence was modified through extra-lemniscal pathways. The models are discussed in the context of previous findings to demonstrate how structural modeling can not only complement, but also extract more information from 2-DG mapping experiments.

Medial cerebellum and long-term habituation of acoustic startle in rats.

Three experiments assessed the effects of damage to the medial cerebellum on long-term habituation (LTH) of the acoustic startle response. Experiment 1 replicated previous results. Lesions of the cerebellar vermis blocked LTH without affecting initial response levels or short-term habituation (STH). The lesions did not disrupt LTH of a simultaneously measured lick-suppression response. In Experiment 2, vermal lesions again blocked LTH of acoustic startle. Control lesions of the cerebellar hemispheres did not affect LTH. In Experiment 3, lesions to the medial (fastigial) cerebellar nuclei blocked LTH. Lesions to the lateral (dentate and interpositus) nuclei did not affect LTH. It is concluded that the medial cerebellum (cortex and nuclei) is part of the essential circuitry for LTH of acoustic startle, whereas the lateral cerebellum is not involved in the basic habituation process.

Medial cerebellum and long-term habituation of acoustic startle in rats.

Medial cerebellum and long-term habituation of acoustic startle 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.

Long-term habituation and sensitization of the acoustic startle response in the normal adult human.

The development and independence of short-term and long-term habituation (and short-term sensitization) of the acoustic startle response to repetitive stimuli has been repeatedly demonstrated in the experimental animal. Although short-term habituation (and sensitization) of acoustic startle has been studied in humans, neither long-term habituation nor sensitization has been demonstrated. In this study, long-term habituation (response amplitude decrement) of the blink component of the acoustic startle response occurred in normal men across five consecutive daily sessions of repetitive acoustic stimulation. Long-term sensitization (onset latency shortening) developed after the third day. Both the long-term habituation and sensitization were independent of the day. Both the long-term habituation and sensitization were independent of the short-term habituation, which developed within each daily session.

Effects of clonidine on habituation and sensitization of acoustic startle in normal, decerebrate and locus coeruleus lesioned rats

Rats were presented with startle-eliciting tones after injection of clonidine (0.01, 0.02, 0.04, 0.08, 0.5, 1.0 or 2.0 mg/kg) or saline. Clonidine potently depressed startle amplitude and the effect was monotonically related todose. Pretreatment with piperoxane (10 mg/kg) antagonized this effect but pretreatment with phentolamine (10 mg/kg) did not. Clonidine still depressed startle in acutely decerebrate rats and in rats with bilateral ablation of the locus coeruleus. Clonidine did not interfere with sensitization to background noise and did not interfere with the ability to startle but instead improved within-session habituation. The results represent one of the few instances in the literature where a drug appears to improve habituation without directly interfering with the ability to respond. The possibility that clonidine might affect startle by stimulating central epinephrine rather than norepinephrine receptors is discussed.