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PubMed1992

Effects of the serotonin releasers 3,4-methylenedioxymethamphetamine (MDMA), 4-chloroamphetamine (PCA) and fenfluramine on acoustic and tactile startle reflexes in rats.

The substituted amphetamines 4-chloroamphetamine (PCA), 3,4-methylenedioxymethamphetamine (MDMA) and fenfluramine (FEN) share the common neurochemical action of acutely releasing central serotonin (5-HT), and yet their behavioral effects are quite different. The present study evaluated the effects of these compounds on acoustic and tactile startle reflexes. PCA and MDMA were qualitatively similar in producing dose-related increases in acoustic and tactile startle reflexes that were slow in onset, but sustained throughout the 3.5-hr test session. Changes in motor activity did not account for the observed excitation of startle. In marked contrast to MDMA and PCA, FEN did not alter tactile startle and tended to depress acoustic startle. The excitatory effect of 20 mg/kg of MDMA was prevented by the 5-HT uptake blockers MDL 27,777A and fluoxetine. MDMA excitation was not affected by a dose of the dopamine antagonist haloperidol that attenuated the startle-enhancing effect of d-amphetamine. MDMA excitation was greatly attenuated by a general depletion of central 5-HT produced by prior intraventricular injection of the 5-HT neurotoxin 5,7-dihydroxytryptamine. PCA and MDMA excitations of startle were attenuated in rats specifically depleted of spinal 5-HT or in rats with radio frequency lesions of the dorsal raphe nucleus. Thus, PCA and MDMA have similar prolonged excitatory effects on startle reflexes that are mediated by ascending (dorsal raphe) and descending (spinal) pathways, whereas FEN differs in its lack of excitation of startle. Differences in the neurochemical properties of these compounds or their patterns of 5-HT release may underlie their different behavioral profiles.

5,7-Dihydroxytryptamine↗
PubMed1990

Spectral frequency and the modulation of the acoustic startle reflex by background noise.

The rat's (Long-Evans) acoustic startle reflex to a high-frequency tone burst (10.5 kHz) was depressed by intense high-frequency band-pass noise (8-16 kHz) but enhanced by low frequency noise (1-2 kHz). However, contrary to the hypothesis that the depression of startle in intense background noise is produced by sensory masking, the reflex to a low-frequency tone burst (at 1 kHz) was depressed by both high- and low-frequency band-pass noise. Two additional hypotheses are offered to supplement sensory masking in order to explain the asymmetry in these data. The first is that the intratympanic reflex, which acts as a high pass filter on acoustic input, is elicited in intense backgrounds. The second is that acoustic startle reflexes elicited by intense low-frequency tones are in part elicited by their high-frequency distortion products and that these distortion products are then masked by high-frequency background noise.

Animals↗
PubMed1998

Psychotropic drugs in breast milk: no evidence for adverse effects on prepulse modulation of startle reflex or on cognitive level in infants.

Reversals in modulation of the startle reflex probably reflect maturational processes in the central nervous system. This study has investigated the longitudinal changes in prepulse modulation of the blink reflex in three groups of individual infants: (a) breast-fed infants of mentally ill mothers who were prescribed selected psychotropic drugs, (b) bottle-fed infants of similarly ill and medicated mothers, and (c) breast-fed infants of healthy control mothers. The acoustic stimulation paradigm and neurophysiological methods were similar to those used in previous studies and, in addition, the infants' development was simultaneously assessed using the Bayley Scales of Infant Development. All the infants were found to be developing normally and across all three groups we observed a clear transition in prepulse modulation of the eye-blink reflex from small inhibition or facilitation in early infancy (1-4 months) to a robust facilitation in middle infancy (5-8 months). This reversal probably reflects the changing balance of developing neural function in normal infants. There were, therefore, no discernible effects in breast-fed infants of exposure to small doses of antidepressant or neuroleptic drugs.

Acoustic Stimulation↗
PubMed2003

Low-frequency tone pips elicit exaggerated startle reflexes in C57BL/6J mice with hearing loss.

The strength of the acoustic startle reflex (ASR) as a function of age was studied in adult C57BL/6J and CBA/CaJ mice, because altered ASR levels are a potential behavioral consequence of the neural reorganization that accompanies the early-onset hearing loss of the C57BL, in contrast to the normal-hearing CBA. For C57BL mice at 14-36 weeks of age, compared with 7-week-old mice, high-frequency thresholds measured with the auditory brainstem response (ABR) were less sensitive by about 25-30 dB while the hearing loss at low frequencies was 10-15 dB, but by 60 weeks losses of 45-50 dB were present across the entire spectrum. Their ASR amplitudes for 16 kHz tone pips were highest at 7 weeks and then declined with age, but, for 4 kHz tones the ASR increased in strength at 18 weeks and beyond to levels above that of the younger mice. This hyperreactivity persisted even in 60-week-old mice. The ASR for 16 kHz stimuli was positively correlated with hearing sensitivity, but the ASR for 4 kHz stimuli was positively correlated with hearing loss for mice that were 18-36 weeks of age. Furthermore, ASR amplitudes for 4 kHz stimuli were positively correlated with the 16 kHz ASR in young C57BL mice but negatively correlated in older mice. There were no similar ASR or ABR changes in adult CBA mice through 19 weeks of age. Correlations between ASR and ABR scores were always weakly positive, and correlations between 4 kHz and 16 kHz ASR amplitudes were always strongly positive. The ASR data in older C57BL mice with hearing loss are consistent with reports describing their increased neural representation of low-frequency sounds and reinforce the value of this strain for studying the functional consequences that accompany age-related cochlear degeneration.

Acoustic Stimulation↗
PubMed1993

Crossed reticular formation connections that mediate the startle reflex in rats.

The startle response is a bilateral response even when elicited by unilateral acoustic or tactile stimuli. Similarly, unilateral electrical stimulation of the reticular formation also elicits a bilateral startle-like response. To examine whether crossed reticular formation connections can distribute the effects of unilateral stimulation across the midline, we delivered one pulse to the caudal pontine (RPC) or medullary reticular formation (MRF) and a second pulse to the opposite side of the brain, at various interpulse intervals. The symmetric collision effects suggest that axons which produce at least 37% (range 23-53%) of the startle response efficacy cross from RPC to RPC with a mean conduction velocity of 13 m/s. Similar collision effects were observed between RPC and MRF sites but at shorter conduction times. To examine which axons might cause these collision effect, the axonally transported label DiI was injected post mortem into 37 RPC sites. Many coarse axons were observed to cross in fascicles between bilateral RPC sites and then separate in the contralateral RPC. The fiber diameters and trajectories of these DiI-labelled axons are consistent with the conduction velocities and trajectories of the substrates mediating the startle-like response determined in collision tests.

Animals↗
PubMed1999

Effect of d-amphetamine on prepulse inhibition of the startle reflex in humans.

RATIONALE: Prepulse inhibition of the startle reflex (PPI) is attenuated in animals after administration of d-amphetamine and other drugs that stimulate mesolimbic dopamine activity. OBJECTIVE: The aim of the present study was to evaluate the effects of d-amphetamine (20 mg) on a variety of psychophysiological and subjective measures, including PPI, in humans. METHOD: Thirty-six participants (18 women) participated in a double-blind, placebo controlled, repeated measures study. In one session, participants received d-amphetamine (20 mg) orally, and in the other session, participants received an identical appearing placebo. Participants were assessed at 60, 90, and 120 min after ingestion with a 5-min block of startle trials (six control trials and six prepulse trials) followed by subjective measures of stimulation and mood. RESULTS: d-Amphetamine increased subjective measures of stimulation and euphoria, attenuated PPI, and increased heart rate, relative to placebo treatment. CONCLUSIONS: The effect of d-amphetamine on the subjective measures was substantial and consistent over time, while the effect on PPI was only observed at 90 min after ingestion, and the effect on heart rate was limited to 90 and 120 min after ingestion.

Affect↗
PubMed1991

Affective individual differences and startle reflex modulation.

Potentiation of startle has been demonstrated in experimentally produced aversive emotional states, and clinical reports suggest that potentiated startle may be associated with fear or anxiety. To test the generalizability of startle potentiation across a variety of emotional states as well as its sensitivity to individual differences in fearfulness, the acoustic startle response of 17 high- and 15 low-fear adult subjects was assessed during fear, anger, joy, sadness, pleasant relaxation, and neutral imagery. Startle responses were larger in all aversive affective states than during pleasant imagery. This effect was enhanced among high fear subjects, although followup testing indicated that other affective individual differences (depression and anger) may also be related to increased potentiation of startle in negative affect. Startle latency was reduced during high- rather than low-arousal imagery but was unaffected by emotional valence.

Emotions↗
PubMed1996

Effect of cigarette smoking on prepulse inhibition of the acoustic startle reflex in healthy male smokers.

The present study investigated the effects of cigarette smoking on prepulse inhibition (PPI) of the acoustic startle reflex in healthy men. Cigarette smoking in a group of overnight smoking-deprived smokers increased PPI as compared to the smoking-deprived condition. This finding is consistent with previous animal studies showing that nicotine increases PPI of the acoustic startle reflex. In addition, cigarette smoking also reduced startle amplitude during the first 6-7 min of the post-smoking session.

Acoustic Stimulation↗
PubMed2004

Prepulse inhibition of the acoustically evoked startle reflex in patients with an acute schizophrenic psychosis--a longitudinal study.

Deficits in sensorimotor gating as assessed by prepulse inhibition (PPI) of the startle reflex have been reported in schizophrenia. However, the state or trait nature of these deficits and the relationships with clinical features and psychopathological symptoms are not clear. To explore these issues, we performed a longitudinal study with schizophrenia inpatients. We examined 36 medicated schizophrenia inpatients twice in the course of an acute psychotic episode: recently after admission and after psychopathological improvement 2-3 weeks later. In addition, we examined 18 healthy control subjects twice (two weeks apart). Relative to control subjects, patients with schizophrenia had lower PPI only in the acute, but not in the improved clinical state. Larger PPI deficits were associated with more severe formal thought disorder and bizarre behavior. In the present longitudinal study, PPI deficits in schizophrenic patients appeared to be state dependent. Taking into account recent evidence from the literature we propose that reduced PPI may be a mediating vulnerability marker of schizophrenia: Impairments in sensorimotor mechanisms which subserve PPI of the startle reflex may both predispose individuals to develop psychosis, and, in addition, may covary with the presence of acute positive symptoms.

Adult↗
PubMed1994

Positive shifts of event-related potentials: a state of cortical disfacilitation as reflected by the startle reflex probe.

Cortical positivity as measured by slow event-related potentials is assumed to represent a decreased excitability of cortical networks and suppression of their behavioral-cognitive output. The blink reflex probe is a commonly used defensive electromyographic response whose amplitude was shown to be modulated by emotional and attentional orientation. It was used here as an indicator of cortico-subcortical excitation. In study 1, 33 healthy subjects took part in a continuous performance test (CPT). Event-related potentials were recorded from 15 standard scalp locations. Acoustic startling noise bursts were delivered during conditions that required either performance of prepared motor responses (Go), inhibition of prepared motor responses (NoGo), or had no motor significance (Irrelevant condition). During the NoGo condition, EEG surface potentials showed a widespread P300-like positivity with a central maximum. Startle responses were inhibited during the NoGo condition as compared to the Irrelevant condition. In study 2 (21 subjects) the same format was used, except that the startle reflex was elicited visually. Startle reflexes again showed smaller magnitude during the NoGo condition, which evoked larger positivity at central sites in comparison to the Irrelevant condition. The relationship between positivity in the EEG and inhibited startle responses is in line with the hypothesis that positive EEG shifts reflect a state of cortical disfacilitation.

Acoustic Stimulation↗
PubMed1997

Startle reflex abnormalities in women with sexual assault-related posttraumatic stress disorder.

OBJECTIVE: This investigation was designed to assess the acoustic startle response in treatment-seeking women with sexual assault-related posttraumatic stress disorder (PTSD). METHOD: Thirteen patients with sexual assault-related PTSD and 16 healthy female comparison subjects were recruited for participation in the study. Each patient met the full criteria for PTSD according to the Structured Clinical Interview for DSM-III-R. All subjects in the study were right-handed. The acoustic stimuli were bursts of white noise (92 dB and 102 dB) with a nearly instantaneous onset delivered binaurally through headphones. RESULTS: The magnitude of the startle response (eye blink) to the first stimulus was asymmetrically distributed in the PTSD patients but not in the comparison subjects: it was greater for the left eye than the right eye in the PTSD patients only. There was a differential asymmetry of startle response in the two subgroups of patients (recent PTSD and long-standing PTSD): the startle reflex was larger for the left eye than the right in the subgroup with recent PTSD but not in the group with long-standing PTSD. CONCLUSIONS: This study provides the first objective evidence of startle abnormalities in women with PTSD. The significantly greater startle responses for the left eye compared with the right in the PTSD subjects suggest a laterality effect. As suggested by the preclinical model of shock sensitization, it is possible that in a subgroup of individuals with PTSD, trauma may sensitize the startle reflex. This model may hold true in humans and is supported by the findings of greater startle response in the patients with recent-onset PTSD.

Acoustic Stimulation↗