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PubMed1992

5-Hydroxytryptamine 1a receptor agonists block prepulse inhibition of acoustic startle reflex.

Presentation of a nonstartling stimulus (prepulse) 100 msec before a startle-eliciting auditory stimulus (pulse) reduces startle reflex amplitude in mammals. Prepulse inhibition of acoustic startle reflex is smaller in schizophrenics than in nonschizophrenics, a phenomenon that has been hypothesized to reflect sensorimotor gating deficits underlying schizophrenic psychosis. Five 5-hydroxytryptamine1a (5-HT1a, serotonin) receptor agonists: 8-hydroxy-2-(di-n-propylamino) tetraline (8-OHDPAT), 5-methoxydimethyltryptamine, buspirone, gepirone and ipsapirone, were tested for effects on prepulse inhibition and startle reflex amplitude in rats. All five agents reduced prepulse inhibition at doses that had no effect on startle reflex amplitude or motor activity. Reduction of prepulse inhibition by 8-OHDPAT was antagonized by (-)propranolol, a 5-HT1a receptor antagonist, and partially by haloperidol, a dopamine D2 receptor antagonist, but not by ketanserin or methysergide, 5-HT2 receptor antagonists. 8-OHDPAT did not reduce prepulse inhibition in subjects pretreated with reserpine or tetrabenazine to deplete neuronal amines, but interpretation of this result is complicated because reserpine and tetrabenazine given alone reduced prepulse inhibition. The results indicate that 5-HT1a receptor agonists block prepulse inhibition of acoustic startle reflex, possibly via dopaminergic mechanisms.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1999

Cross-species studies of sensorimotor gating of the startle reflex.

Sensorimotor gating of the startle reflex can be assessed across species, using similar stimuli to elicit comparable response characteristics. As measured by prepulse inhibition (PPI), gating is reduced in patients with some neuropsychiatric disorders, and in rats after manipulations of limbic cortex, striatum, pallidum, or pontine tegmentum. This limbic "CSPP" circuitry can be studied in rats to reveal the neurochemical and neuroanatomical substrates regulating PPI at a high level of resolution. This detailed circuit information is used as a "blueprint" to identify substrates that may lead to PPI deficits in psychiatric-disordered humans. Some human disorders with identifiable, localized lesions in CSPP circuitry, for example, Huntington's disease, provide direct validation for this cross-species model. Studies have begun to assess the pharmacological homology of PPI across species, as an initial step towards translating detailed neural circuit information from rats to humans. These initial studies suggest the possibility that the effects of dopaminergic (DAergic) drugs on PPI (reducing PPI) may be homologous across species; nicotinic drugs may also produce similar effects on PPI across species (increasing PPI). By contrast, the effects of glutamatergic and serotonergic drugs may exhibit disparate effects on PPI across species. The use of DAergic agonists in human studies is complicated by their significant side effects, but new studies demonstrate that several "human friendly" direct DA agonists disrupt PPI in rats and are thus good candidates for further studies of the cross-species homology of the DAergic regulation of PPI. In this manner, PPI can be used to probe the sensitivity of DAergic systems, and perhaps other CSPP elements, across normal and neuropsychiatric-disordered populations.

Animals↗

PubMed2001

Conditioned brain-stimulation reward attenuates the acoustic startle reflex in rats.

The acoustic startle reflex (ASR) in rats is attenuated by a light paired with food or, in humans, by "pleasant" pictures. Rats were trained to barpress for lateral hypothalamus (LH) stimulation. ASR amplitudes were then measured at 4 intensities, with or without a light. Control rats that did not receive brain-stimulation reward (BSR) showed initially lower ASR amplitudes than did rats exposed to BSR, but both groups responded similarly with or without light. Next, experimental rats were given BSR in the presence of light but not in its absence. After conditioning, ASR amplitudes were reduced, and ASR thresholds were raised by a mean of 2.6 dB in the light but remained at preconditioning levels without light. No such change was found for control rats or rats with placements outside the LH.

Acoustic Stimulation↗

PubMed2000

Abnormalities of the acoustic startle reflex and reaction time in gilles de la tourette syndrome.

OBJECTIVE: To study the startle reflex and the effect of the startle reflex stimulus over reaction time (start-react effect) in Gilles de la Tourette syndrome (GTS). METHOD: Ten GTS patients and ten matched healthy volunteers underwent a simple RT paradigm (4 blocks of 50 trials). Forty acoustic startle reflex stimuli (110 dB) were randomly delivered with a 20% occurrence probability and presented unexpectedly at the same time as the imperative stimuli of the RT. Variables of interest were: amplitude, onset latency, degree of spread and rate of habituation of the startle response, and RT and the start-react effect caused by the startle stimuli. RESULTS: GTS patients showed a significantly higher amplitude, a major degree of spread and fewer habituation phenomena of the startle reflex. GTS patients showed poorer non statistically significant RT performance compared to controls, with a significant correlation between RT and severity of the disease. The start-react effect was significantly less pronounced in GTS patients. CONCLUSIONS: The present study confirms that GTS has an exaggerated startle reflex response and extend the spectrum of abnormalities to the start-react effect. A state of dopaminergic hyperactivity may have contributed to these results.

Adolescent↗

PubMed1993

Collision-like interactions between acoustic and electrical signals that produce startle reflexes in reticular formation sites.

A startle-like response can be evoked at low currents by one-pulse electrical stimulation of reticular formation sites from the rostrolateral pons to the caudomedial medulla. To test whether this response is mediated by the same reticular formation neurons as those that mediate the acoustic startle, we delivered a brief, subthreshold acoustic stimulus followed by an 0.1-ms electrical pulse to one side of the reticular formation of rats. The current thresholds for electrical startle were usually powerfully reduced (50-80%) whenever the acoustic stimulation was presented within 5 ms of the electrical pulse. This summation was, however, interrupted by brief (0.2-1.0 ms) spike-like increases in threshold when the electrical pulse was delivered 4.0-4.6 ms after the offset of the acoustic stimulus. The timing of the spike-like increase in threshold shifted to longer intervals in more caudal sites, consistent with the conduction of action potentials in the startle pathway. For example, the increase occurred at an interval of 4.1 ms near the ventral lateral lemniscus (VLL) and at intervals of 4.4-4.6 ms for sites in the pontine or medullary reticular formation. The increases in startle threshold are attributed to collisions between antidromic action potentials evoked by the electrical pulses and orthodromic action potentials evoked by the acoustic stimuli. These results suggest that the neurons in reticular formation that produce the acoustic startle reflex overlap greatly with the neurons that mediate electrically evoked startle-like responses. Also, the acoustic signals mediating the startle reflex must be, in large part, a synchronous volley of action potentials conducted by longitudinal bundles of reticular formation axons.

Acoustic Stimulation↗

PubMed2005

Apomorphine effects on emotional modulation of the startle reflex in rats.

RATIONALE: Emotional modulation of the startle reflex in the rat may be used to assess whether activation of dopamine receptors specifically increases hedonia, incentive, fear or arousal. OBJECTIVES: The objective of the study is to determine the effects of apomorphine (0.8 mg/kg s.c.) on the startle reflex of rats (72 male Sprague-Dawley rats) exposed to one of three affective conditions. These conditions were negative affective stimulus (exposure to cat smell), positive affective stimulus (availability of a 20% sucrose solution), neutral stimulus (no additional affective stimulus) and one of two appetitive "drive" states (food deprived or non-food deprived). METHODS: The startle response (whole-body flinch response) was measured after presentation of a range of intensities of acoustic stimuli (65-120 dB, 40-ms duration white noise). The resulting sigmoidal stimulus intensity-response magnitude (SIRM) curves were fitted using a logistic regression procedure, and features of these functions were abstracted for analysis. RESULTS: Maximal startle amplitudes were increased by the negative affect (fear) stimulus in non-food-deprived rats and decreased by the positive affect stimulus in food-deprived rats. Apomorphine mimicked the effects of food deprivation under both affect conditions, but also produced an effect in food-deprived rats similar to that of the positive affect condition. CONCLUSIONS: The results are consistent with both a positive incentive effect and a direct hedonic action of apomorphine, but inconsistent with a role in general arousal. In addition, a method of analysing SIRM functions with logistic regressions is introduced as a useful means of standardising startle reflex measurements.

Acoustic Stimulation↗

PubMed1991

Effects of nicotine on the acoustic startle reflex amplitude in rats.

The acoustic startle reflex was used to measure changes in sensorimotor reactivity in response to nicotine administration and cessation. Male rats received saline, 6 mg/kg/day or 12 mg/kg/day nicotine delivered subcutaneously by osmotic minipumps. The pumps delivered their contents during a 10-day period of implantation, after which time they were explanted. Animals were tested for startle reflex amplitudes using two levels of white noise bursts prior to pump implantation, on days 1 and 7 of nicotine or saline administration, and on several days following drug cessation. Nicotine produced a dose-dependent increase in startle amplitude during the period of administration that decreased during cessation. Results are interpreted in terms of nicotine's actions to enhance attentional processes.

Acoustic Stimulation↗

PubMed1994

[A study of pathogenesis and symptoms of Tourette's syndrome--mainly on the importance of "startle reflex" through Latah reaction].

There is no established theory on pathogenesis of Tourette's syndrome, but recently, a theory of the British school of behaviorism; 'transient tics' and the more serious case, Tourette's syndrome which ensues on the fixation of the startle reflex, have received attention. So we determined, whether pathogenesis and symptoms of Tourette's syndrome could be systematically explained by "the startle reflex theory". Authors assumed that the startle reflex was composed of two divided actions, a series of muscular movements which started with eye blinks and terminated in the flexion of lower limbs (the primary startle reflex system), and more purposeful and complicated actions which occasionally arose from these movements (the secondary startle reflex system). On the basis of this supposition, we considered simple tics which are usually called "tics", those are the manifestation of astonishment by the primary startle reflex system, and complex tics; echo phenomena, coprolalia, complex movements, and so on, which are said to be pathognomonic of Tourette's syndrome, are the expression of amazement by the secondary startle reflex system. Furthermore, we formulated a hypothesis that in the latter case, the secondary startle reflex system contains the senses of orientation and defense, and the defense mechanism which is innately imprinted in common throughout human race, and covered through individual development, is released and fixed in the form of complex movements or echo phenomena in an emergency, such as astonishment. To discuss further, we determined Latah reaction minutely (especially in "Imu" of the Ainu race in Japan) in which intricate symptoms had been suggested as one of the senses of defense, were closely related to Tourette's syndrome. For more concrete study, we presented two severe cases of Tourette's syndrome. Considering the circumstances mentioned above, pathogenesis and symptoms of Tourette's syndrome could be explained by the startle reflex theory. Finally, we analyzed several psychiatrical syndromes which were provoked by astonishment, we concluded that it was necessary to emphasize Tourette's syndrome was only a part of those more comprehensive syndromes which could be called "startle syndromes".

Adult↗

PubMed2001

The relationship between prepulse detection and prepulse inhibition of the acoustic startle reflex.

Prepulse inhibition (PPI) of the startle reflex is defined as the attenuation of the startle response to a startling stimulus (pulse), when such a stimulus is briefly preceded by a stimulus of subthreshold intensity (prepulse). PPI is thought to be neither learned nor due to conscious response inhibition, as it occurs at stimulus onset asynchronies (SOAs) too short to enable the activation of a volitional response. The present study explored the latter of these assertions by investigating (a) the degree to which human subjects are able to detect prepulses at SOAs of 30, 60 and 120 ms, and (b) whether such detection is related to inhibition. Startle eyeblink reflex and detection were measured in 39 participants subjected to an acoustic startle paradigm. Results revealed a significant trend in prepulse detection according to SOA, with highest detection rates at the 120-ms SOA (75%). However, trials on which detection occurred did not differ from trials without detection on measures of startle inhibition. This suggests that PPI is independent of awareness of the prepulse.

Acoustic Stimulation↗

PubMed2004

Plasticity of the acoustic startle reflex in currently abstinent ecstasy (MDMA) users.

RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is neurotoxic upon central serotonin systems in experimental animals and probably also in humans. Serotonin is involved in the habituation, sensitization and prepulse inhibition (PPI) of the startle reflex. OBJECTIVES: To study the plasticity of startle reflex in currently abstinent MDMA users. METHODS: Electromyographic responses to acoustic startle stimuli (pulse alone and prepulse-pulse trials) were recorded in 23 currently abstinent ecstasy users and 20 matched control subjects. Depending on the extent of their previous drug use ecstasy users were divided into two groups [life-time dose <90 (n=11) and > or =90 pills (n=12), respectively]. RESULTS: There were no significant differences in habituation, sensitization or PPI of the startle reflex between the entire group of ecstasy users and controls. However, sensitization of the startle reflex was stronger in the > or =90 compared with either the <90 MDMA pills or the control group. Correlations between patterns of drug use and startle parameters did not reach the level of significance, although users with a younger age at the onset of MDMA (and other drug) use tended to present with higher sensitization of the startle reflex. CONCLUSIONS: Heavy users of MDMA (and other recreational drugs) present with strong sensitization of the startle reflex. Nevertheless, it is unclear whether this finding is secondary to the use of MDMA and its well-recognized neurotoxic potential. Alternatively, strong sensitization might reflect a pre-existing trait predisposing to drug use. A clearer picture of the impact of ecstasy on startle plasticity may be obtained from longitudinal investigations.

Adult↗

PubMed1993

Emotion in the criminal psychopath: startle reflex modulation.

Startle-elicited blinks were measured during presentation of affective slides to test hypotheses concerning emotional responding in psychopaths. Subjects were 54 incarcerated sexual offenders divided into nonpsychopathic, psychopathic, and mixed groups based on file and interview data. Consistent with findings for normal college students, nonpsychopaths and mixed subjects showed a significant linear relationship between slide valence and startle magnitude, with startle responses largest during unpleasant slides and smallest during pleasant slides. This effect was absent in psychopaths. Group differences in startle modulation were related to affective features of psychopathy, but not to antisocial behavior per se. Psychopathy had no effect on autonomic or self-report responses to slides. These results suggest an abnormality in the processing of emotional stimuli by psychopaths that manifests itself independently of affective report.

Adult↗

PubMed1977

Psilocybin: biphasic dose-response effects on the acoustic startle reflex in the rat.

The startle reflex was measured in 7 groups of 10 rats each after intraperitoneal injection of saline or 0.25, 0.50, 0.75, 1.0, 2.0, 4.0 or 8.0 mg/kg psilocybin. Low doses (0.75-2.0 mg/kg) increased startle amplitude whereas high doses (4.0-8.0 mg/kg) depressed startle. Selected low (0.71 mg/kg) or high (5.70 mg/kg) doses of psilocin also had a biphasic dose-response effect on startle comparable in magnitude to equimolar doses of psilocybin. This biphasic dose-response relationship of the indole hallucinogen, psilocybin, on startle is consistent with the hypothesis that startle is increased when the firing rates of midbrain raphe neurons are selectively inhibited but is depressed when neurons postsynaptic to raphe cells are also inhibited.

Acoustic Stimulation↗

PubMed2005

Chronic cannabis use is associated with attention-modulated reduction in prepulse inhibition of the startle reflex in healthy humans.

Regardless of a wide research interest the nature of a relationship between cannabis use and schizophrenia is controversial. One of the physiological abnormalities in schizophrenia is attention-modulated deficit in prepulse inhibition (PPI), which is a normal reduction in the startle reflex magnitude when a non-startling stimulus (prepulse) precedes the startling stimulus (pulse). This experiment was designed to determine whether or not otherwise healthy people using cannabis would exhibit attention-modulated deficit in PPI. The startle reflex was recorded in carefully screened healthy humans attending to and ignoring auditory pulse and prepulse stimuli separated by short (20-200 ms) and long prepulse intervals (1600 ms). In contrast to 12 non-using controls, cannabis use in 16 healthy humans was associated with significant reduction in%PPI while attending to auditory stimuli, but not while ignoring them. The PPI was correlated with the duration of cannabis use but not with the concentration of cannabinoid metabolites in urine and the recency of cannabis use in the preceding 24 hours. Cannabis use was not associated with changes in prepulse facilitation of startle reflex magnitude (%PPF) at long prepulse intervals, prepulse facilitation of startle reflex latency and startle reflex magnitude in the absence of prepulses. These results suggest that chronic, but not acute, use of cannabis is associated with schizophrenia-like disruption in PPI in healthy controls. Such reduction in PPI is attention-dependent and does not reflect a global deficit in sensorimotor gating in cannabis users.

Acoustic Stimulation↗

PubMed2003

A review of the modulation of the startle reflex by affective states and its application in psychiatry.

OBJECTIVE: To provide an overview of startle reflex methodologies applied to the examination of emotional and motivational states in humans and to review the findings in different forms of psychopathology. METHODS: Pertinent articles were searched mostly via MEDLINE and PsycINFO. RESULTS: The startle reflex is a non-invasive translational tool of research that bridges the gap between animal and human investigations. Startle is used to study fear and anxiety, affective disturbances, sensitization, motivational states, and homeostasis. CONCLUSIONS: The startle reflex is highly sensitive to various factors that are of interest in the studies of emotional disorders and has promoted new areas of investigations in psychiatry. However, research in psychiatry is still in its infancy and most findings await replication. Future progress will benefit from the development of innovative and powerful designs tailored to investigate specific disorders. SIGNIFICANCE: The startle reflex has utility as a research tool to examine trauma-related disorders, fear learning, drug addiction, and to contrast affective states and emotional processing across diagnostic groups, but its usefulness as a diagnostic tool is limited.

Animals↗

PubMed1994

Emotional qualities of odors and their influence on the startle reflex in humans.

Recent human and animal research suggests that the startle reflex might serve as a psychophysiological indicator of the emotional valence of foreground stimulation. The present experiment was designed to evaluate the emotional effects of positive and negative odorant stimuli. We examined the effects of continuous hydrogen sulphide (H2S) and vanillin stimulation on the magnitude of the acoustic startle reflex (measured at the M. orbicularis oculi) and on ratings of subjective valence in 16 healthy subjects. In accordance with the view that odors have emotional qualities, we found that H2S, a presumed negative foreground stimulus, significantly enhanced the startle-reflex amplitude relative to neutral air stimulation, whereas vanillin, a positive foreground stimulus, tended to reduce the reflex amplitude compared with neutral air stimulation. Both odorant stimuli were rated as equally intense by the subjects, and heart rate and electrodermal activity were not affected differentially by the two odorants.

Acoustic Stimulation↗

PubMed2006

Neural circuits containing pallidotegmental GABAergic neurons are involved in the prepulse inhibition of the startle reflex in mice.

BACKGROUND: Prepulse inhibition (PPI) of the startle response is a measure of the inhibitory function and time-linked information processing by which a weak sensory stimulus (the prepulse) inhibits the startle response caused by a sudden intense stimulus. We attempted to clarify the neuronal circuits underlying the control of PPI of the startle reflex in mice. METHODS: c-Fos immunohistochemistry was used to detect neurons activated by startle pulse and/or prepulse trials. Behavioural pharmacology and tracing studies were also conducted. RESULTS: The lateral globus pallidus (LGP) was activated by prepulses. Activation of the caudal pontine reticular nucleus (PnC) evoked by the startle pulses was inhibited under PPI conditions. Double-immunostaining revealed that c-Fos-positive cells in the LGP following prepulse trials were GABAergic neurons. Bilateral microinjections of lidocaine into the LGP resulted in an impairment of PPI. Fluoro-gold infusion into the PnC and the pedunculopontine tegmental nucleus (PPTg) retrogradely labeled neurons in the PPTg and LGP, respectively. Microinjections of phaclofen into the PPTg significantly impaired PPI. CONCLUSIONS: These results suggest that GABAergic neurons in the LGP which project to the PPTg play a crucial role through the activation of GABAB receptors in the regulation of PPI of the startle reflex in mice.

Acoustic Stimulation↗

PubMed1996

Exaggerated acoustic startle reflex in Gulf War veterans with posttraumatic stress disorder.

OBJECTIVE: Exaggerated startle reflex is reputed to be one of the cardinal symptoms of posttraumatic stress disorder (PTSD). The goal of this study was to assess the magnitude of the acoustic startle reflex in Gulf War veterans with PTSD. METHOD: The eye-blink component of the startle reflex was measured in response to six blocks of pseudorandomized 40-msec white noise bursts of varying intensities (90, 96, 102, 108, and 114 dB) in 10 Gulf War veterans with PTSD, seven Gulf War veterans without PTSD, and 15 civilian subjects without PTSD. RESULTS: The magnitude of the first startle response, as well as the magnitude of startle response averaged across blocks of testing, was significantly greater in Gulf War veterans with PTSD than in veteran and civilian comparison groups. CONCLUSIONS: Consistent with some clinical studies investigating the startle response in Vietnam veterans with PTSD, this investigation provides evidence for exaggerated startle response in this disorder. Preclinical studies of shock sensitization of the startle response suggest that the higher levels of startle response seen in the PTSD subjects may reflect a sensitization of the fear/alarm response created by the stress of combat trauma.

Acoustic Stimulation↗

PubMed1997

Olfactory bulbectomy enhances sensitization of the acoustic startle reflex produced by acute or repeated stress.

The effects of olfactory bulbectomy on the acoustic startle reflex and shock-induced sensitization of the startle reflex were examined in 3 experiments. In Experiment 1, bulbectomized animals showed a modest increase in baseline startle responding following surgery, and normal acquisition of fear-potentiated startle, but a pronounced increase in baseline startle responding during the course of conditioning relative to sham-operated controls. In Experiments 2 and 3, bulbectomized animals showed shock-induced sensitization of the startle reflex to shock intensities that did not produce sensitization in sham and unoperated controls. These data suggest that olfactory bulbectomy results in an increased vulnerability to stressors, which may be mediated by a disinhibition of the amygdala or other structures involved in mediating stress and anxiety. Thus, the olfactory bulbectomy model of depression may share some similarities with other stress-induced models of depression.

Acoustic Stimulation↗