Acoustic Startle Response Amplitude Research Articles

Alpha9alpha10 knockout mice show altered physiological and behavioral responses to signals in masking noise.

Medial olivocochlear (MOC) efferents modulate outer hair cell motility through specialized nicotinic acetylcholine receptors to support encoding of signals in noise. Transgenic mice lacking the alpha9 subunits of these receptors (α9KOs) have normal hearing in quiet and noise, but lack classic cochlear suppression effects and show abnormal temporal, spectral, and spatial processing. Mice deficient for both the alpha9 and alpha10 receptor subunits (α9α10KOs) may exhibit more severe MOC-related phenotypes. Like α9KOs, α9α10KOs have normal auditory brainstem response (ABR) thresholds and weak MOC reflexes. Here, we further characterized auditory function in α9α10KO mice. Wild-type (WT) and α9α10KO mice had similar ABR thresholds and acoustic startle response amplitudes in quiet and noise, and similar frequency and intensity difference sensitivity. α9α10KO mice had larger ABR Wave I amplitudes than WTs in quiet and noise. Other ABR metrics of hearing-in-noise function yielded conflicting findings regarding α9α10KO susceptibility to masking effects. α9α10KO mice also had larger startle amplitudes in tone backgrounds than WTs. Overall, α9α10KO mice had grossly normal auditory function in quiet and noise, although their larger ABR amplitudes and hyperreactive startles suggest some auditory processing abnormalities. These findings contribute to the growing literature showing mixed effects of MOC dysfunction on hearing.

Auditory Behavior in Adult-Blinded Mice.

Cross-modal plasticity occurs when the function of remaining senses is enhanced following deprivation or loss of a sensory modality. Auditory neural responses are enhanced in the auditory cortex, including increased sensitivity and frequency selectivity, following short-term visual deprivation in adult mice (Petrus et al. Neuron 81:664-673, 2014). Whether or not these visual deprivation-induced neural changes translate into improved auditory perception and performance remains unclear. As an initial investigation of the effects of adult visual deprivation on auditory behaviors, CBA/CaJ mice underwent binocular enucleation at 3-4weeks old and were tested on a battery of learned behavioral tasks, acoustic startle response (ASR), and prepulse inhibition (PPI) tests beginning at least 2weeks after the enucleation procedure. Auditory brain stem responses (ABRs) were also measured to screen for potential effects of visual deprivation on non-behavioral hearing function. Control and enucleated mice showed similar tone detection sensitivity and frequency discrimination in a conditioned lick suppression test. Both groups showed normal reactivity to sound as measured by ASR in a quiet background. However, when startle-eliciting stimuli were presented in noise, enucleated mice showed decreased ASR amplitude relative to controls. Control and enucleated mice displayed no significant differences in ASR habituation, PPI tests, or ABR thresholds, or wave morphology. Our findings suggest that while adult-onset visual deprivation induces cross-modal plasticity at the synaptic and circuit levels, it does not substantially influence simple auditory behavioral performance.

Role of GluA4 in the acoustic and tactile startle responses

The primary startle response (SR) is an innate reaction evoked by sudden and intense acoustic, tactile or visual stimuli. In rodents and humans the SR involves reflexive contractions of the face, neck and limb muscles. The acoustic startle response (ASR) pathway consists of auditory nerve fibers (AN), cochlear root neurons (CRNs) and giant neurons of the caudal pontine reticular nucleus (PnC), which synapse on cranial and spinal motor neurons. The tactile startle response (TSR) is transmitted by primary sensory neurons to the principal sensory (Pr5) and spinal (Sp5) trigeminal nuclei. The ventral part of Pr5 projects directly to the PnC neurons. The SR requires rapid transmission of sensory information to initiate a fast motor response. Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR) are necessary to transmit auditory information to the PnC neurons and elicit the SR. AMPARs containing the glutamate AMPAR subunit 4 (GluA4) have fast kinetics, which makes them ideal candidates to transmit the SR signal. This study examined the role of GluA4 within the primary SR pathway by using GluA4 knockout (GluA4-KO) mice. Deletion of GluA4 considerably decreased the amplitude and probability of successful ASR and TSR, indicating that the presence of this subunit is critical at a common station within the startle pathway. We conclude that deletion of GluA4 affects the transmission of sensory signals from acoustic and tactile pathways to the motor component of the startle reflex. Therefore, GluA4 is required for the full response and for reliable elicitation of the startle response.

Phasic activation of the locus coeruleus attenuates the acoustic startle response by increasing cortical arousal

An alerting sound elicits the Acoustic Startle Response (ASR) that is dependent on the sound volume and organisms’ state, which is regulated by neuromodulatory centers. The locus coeruleus (LC) neurons respond to salient stimuli and noradrenaline release affects sensory processing, including auditory. The LC hyperactivity is detrimental for sensorimotor gating. We report here that priming microstimulation of the LC (100-ms at 20, 50, and 100 Hz) attenuated the ASR in rats. The ASR reduction scaled with frequency and 100 Hz-stimulation mimicked pre-exposure to a non-startling tone (prepulse). A rapid (~ 40 ms) EEG desynchronization following the LC stimulation suggested that the ASR reduction was due to elevated cortical arousal. The effects of LC stimulation on the ASR and EEG were consistent with systematic relationships between the ASR, awake/sleep state, and the cortical arousal level; for that matter, a lower ASR amplitude corresponded to a higher arousal level. Thus, the LC appears to modulate the ASR circuit via its diffuse ascending projections to the forebrain saliency network. The LC modulation directly in the brainstem and/or spinal cord may also play a role. Our findings suggest the LC as a part of the brain circuitry regulating the ASR, while underlying neurophysiological mechanisms require further investigation.

Comparing Perika St. John’s Wort and Sertraline for Treatment of Posttraumatic Stress Disorder in Mice

Posttraumatic stress disorder (PTSD) is a serious mental health condition that affects some individuals who have witnessed or experienced a life-threatening or traumatic event. An enhanced or exaggerated acoustic startle response (ASR), reflecting heightened sensitivity to unexpected, loud sound, is a hallmark symptom of PTSD. Antidepressant medications, such as sertraline, are first-line pharmacotherapeutic agents in the treatment of PTSD, but concerns about potential side effects or taking synthetic drugs prompt discovery of naturalistic therapeutic agents. This study examined the relative effectiveness of a compound containing St. John’s Wort (SJW), an herb widely prescribed for depression in Europe and sold as a dietary supplement in the United States, compared to sertraline (Zoloft) in a mouse model of PTSD. Thirty-six mice were tested for baseline ASR, then they were exposed to rats in a predator exposure paradigm known to induce PTSD-like symptoms. Mice were randomly divided into three groups for treatment (control, sertraline, SJW), and ASR was retested one week later. One-way ANOVAs found no significant group differences in ASR amplitude at baseline but a significant effect of Treatment Group after predator exposure, F(2, 33) = 5.645, p = .008, n2 = .225, when SJW-treated mice had ASR amplitudes that were significantly lower than sertraline-treated mice (by 27%) and controls (by 26%). Fecal boli counts showed a similar pattern, with lowest counts in SJW-treated mice. These results suggest SJW could be considered for studies of PTSD treatment in humans as well.

Pyrethroid neurotoxicity studies with bifenthrin indicate a mixed Type I/II mode of action.

BACKGROUNDBifenthrin is usually considered a Type I pyrethroid, because it lacks an α‐CN group present in Type II pyrethroids, but some previous studies suggest a mixed Type I/II mode‐of‐action. Results are presented for bifenthrin in a rat developmental neurotoxicity (DNT) study along with effects on Na currents in human VGSC subtypes. Molecular modeling comparisons were also made for bifenthrin and other pyrethroids.RESULTSIn a rat DNT study, bifenthrin produced tremors and clonic convulsions in dams and pups and slightly reduced acoustic startle response amplitude, and increased Tmax, at PND20 in females. Similar blood levels of bifenthrin were measured in dams and pups at each dose level i.e. no concentration in pups. In human VGSC experiments, using the Nav1.8 subtype, bifenthrin's effects on inactivation were slight, as for Type II pyrethroids, but without large prolongation of the tail current (deactivation) seen with Type II. Molecular modeling of bifenthrin indicates that the o‐Me group may occupy a similar space to the α‐CN group of cypermethrin and fenpropathrin.CONCLUSIONIn a DNT study and on human Nav1.8 tail currents bifenthrin showed Type I and II effects, similar to some published studies. Overall, bifenthrin acts as a mixed Type I/II pyrethroid. © 2018 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Relationships between the acoustic startle response and prepulse inhibition in C57BL/6J mice: a large-scale meta-analytic study

Prepulse inhibition (PPI) is the suppression of a startle reflex response to a startle stimulus that occurs when a weak prepulse stimulus precedes the startle stimulus. PPI is measured to assess sensorimotor gating across species, including humans and rodents. Reduced PPI, which is thought to reflect dysfunction of sensorimotor gating, is reported in patients with psychiatric disorders, such as schizophrenia, bipolar disorder, and post-traumatic stress disorder (PTSD), and in animal models of these disorders. Individual differences in basal startle reactivity occur even in a genetically homogenous group of animals; however, there is limited information regarding whether basal levels of the startle response are associated with variations in PPI levels. Here, to explore the relationship between an acoustic startle response (ASR) and PPI, we performed a meta-analysis of data obtained from more than 1300 C57BL/6J male mice on the influence of an ASR to 110- and 120-dB startle stimuli on the PPI levels of the ASR at 74- and 78-dB prepulse intensities. Examination of scatter plots of the ASR amplitudes and PPI levels followed by correlation analyses indicated that there is no simple linear relationship between the two measures; when mice were divided into three groups on the basis of their startle amplitudes, there were positive correlations between the amplitude of the ASR to the 110-dB stimulus and PPI levels in a group of mice that showed lower ASR amplitudes among the genetically homogenous group, whereas no significant correlations were identified in groups of mice that showed intermediate and higher ASR amplitudes. As indicated by the correlation analysis, the lowest responders to the 110-dB stimulus exhibited lower levels of PPI than the intermediate or higher responders. In contrast, for the 120-dB stimulus, a negative correlation was identified between the amplitude of the ASR to the 120-dB stimulus and the PPI levels in the groups of mice that showed intermediate or higher ASR amplitudes. Lower and intermediate responders showed higher levels of PPI than higher responders to the 120-dB stimulus. These findings suggest that basal startle reactivity may affect PPI levels in male C57BL/6J mice, thus representing one potential confounding factor that may confuse the interpretation of PPI results. These findings emphasize the importance of careful examination of startle reactivity to ensure a reliable assessment of PPI.

Genetically defined fear-induced aggression: Focus on BDNF and its receptors

Brain-derived neurotrophic factor (BDNF), its precursor proBDNF, BDNF pro-peptide, BDNF mRNA levels, as well as TrkB and p75NTR receptors mRNA and protein levels, were studied in the brain of rats, selectively bred for more than 85 generations for either the high level or the lack of fear-induced aggressive behavior. Furthermore, we have found that rats of aggressive strain demonstrated both high level of aggression toward humans and increased amplitude of acoustic startle response compared to rats selectively bred for the lack of fear-induced aggression. Significant increase in the BDNF mRNA, mature BDNF and proBDNF protein levels in the raphe nuclei (RN), hippocampus (Hc), nucleus accumbens (NAcc), amygdala, striatum and hypothalamus (Ht) of aggressive rats was revealed. The BDNF/proBDNF ratio was significantly reduced in the Hc and NAcc of highly aggressive rats suggesting prevalence of the proBDNF in these structures. In the Hc and frontal cortex (FC) of aggressive rats, the level of the full-length TrkB (TrkB-FL) receptor form was decreased, whereas the truncated TrkB (TrkB-T) protein level was increased in the RN, FC, substantia nigra and Ht. The TrkB-FL/TrkB-T ratio was significantly decreased in highly aggressive rats suggesting TrkB-T is predominant in highly aggressive rats. The p75NTR expression was slightly changed in majority of studied brain structures of aggressive rats. The data indicate the BDNF system in the brain of aggressive and nonaggressive animals is extremely different at all levels, from transcription to reception, suggesting significant role of BDNF system in the development of highly aggressive phenotype.

COMT Genotype and Sensory and Sensorimotor Gating in High andLow Hypnotizable Subjects

We investigated the association between hypnotizability, COMT polymorphism, P50 suppression ratio, and prepulse inhibition of acoustic startle response (ASR) in 21 high (HH) and 19 low (LH) hypnotizable subjects. The frequency of Met/Met carriers of COMT polymorphysm was higher in HH than in LH group (33.3% versus 10.6%, p = .049). Increased ASR amplitude and latency and decreased prepulse inhibition at 120 ms lead interval were found in the HH compared to the LH group. The effect of COMT genotype on prepulse inhibition was observed in LH group only. No between-group differences in P50 measures were found. The obtained results suppose the participation of dopamine system in mechanisms of hypnotizability and different allocation of attentional resources in HH and LH subjects.

Traumatic brain injury impairs sensorimotor function in mice

IntroductionUnderstanding the extent to which murine models of traumatic brain injury (TBI) replicate clinically relevant neurologic outcomes is critical for mechanistic and therapeutic studies. We determined sensorimotor outcomes in a mouse model of TBI and validated the use of a standardized neurologic examination scoring system to quantify the extent of injury. Materials and methodsWe used a lateral fluid percussion injury model of TBI and compared TBI animals to those that underwent sham surgery. We measured neurobehavioral deficits using a standardized 12-point neurologic examination, magnetic resonance imaging, a rotating rod test, and longitudinal acoustic startle testing. ResultsTBI animals had a significantly decreased ability to balance on a rotating rod and a marked reduction in the amplitude of acoustic startle response. The neurologic examination had a high inter-rater reliability (87% agreement) and correlated with latency to fall on a rotating rod (Rs = −0.809). ConclusionsTBI impairs sensorimotor function in mice, and the extent of impairment can be predicted by a standardized neurologic examination.

Elevated Acoustic Startle Responses in Humans: Relationship to Reduced Loudness Discomfort Level, but not Self-Report of Hyperacusis.

Increases in the acoustic startle response (ASR) of animals have been reported following experimental manipulations to induce tinnitus, an auditory disorder defined by phantom perception of sound. The increases in ASR have been proposed to signify the development of hyperacusis, a clinical condition defined by intolerance of normally tolerable sound levels. To test this proposal, the present study compared ASR amplitude to measures of sound-level tolerance (SLT) in humans, the only species in which SLT can be directly assessed. Participants had clinically normal/near-normal hearing thresholds, were free of psychotropic medications, and comprised people with tinnitus and without. ASR was measured as eyeblink-related electromyographic activity in response to a noise pulse presented at a range of levels and in two background conditions (noise and quiet). SLT was measured as loudness discomfort level (LDL), the lowest level of sound deemed uncomfortable, and via a questionnaire on the loudness of sounds in everyday life. Regardless of tinnitus status, ASR amplitude at a given stimulus level increased with decreasing LDL, but showed no relationship to SLT self-reported via the questionnaire. These relationships (or lack thereof) could not be attributed to hearing threshold, age, anxiety, or depression. The results imply that increases in ASR in the animal work signify decreases in LDL specifically and may not correspond to the development of hyperacusis as would be self-reported by a clinic patient.

Development of the acoustic startle response in rats and its change after early acoustic trauma

Even brief acoustic trauma during the critical period of development that results in no permanent hearing threshold shift may lead to altered auditory processing in adulthood. By monitoring the acoustic startle response (ASR), we examined the development of auditory function in control rats and in rats exposed to intense noise at the 14th postnatal day (P14). First ASRs appeared on P10–P11 to intense low-frequency tones. By P14, the range of sound intensities and frequencies eliciting ASRs extended considerably, the ASR reactivity being similar at all frequencies (4–32kHz). During the subsequent two weeks, ASR amplitudes to low-frequency stimuli (4–8kHz) increased, whereas the ASRs to high-frequency tones were maintained (16kHz) or even decreased (32kHz). Compared to controls, noise exposure on P14 (125dB SPL for 8, 12, or 25min) produced transient hyper-reactivity to startle stimuli, manifested by a decrease of ASR thresholds and an increase of ASR amplitudes. ASR enhancement occurred regardless of permanent hearing loss and was more pronounced at high frequencies. The hyper-reactivity of ASRs declined by P30; the ASR amplitudes in adult exposed rats were lower than in controls. The histological control did not reveal loss of hair cells in adult exposed rats, however, the number of inner hair cell ribbon synapses was significantly decreased, especially in the high-frequency part of the cochlea. The results indicate that early acoustic trauma may result in complex changes of ASRs during development.

The effects of Eph–ephrin mutations on pre-pulse inhibition in mice

Eph–ephrin signaling is known to be important in directing topographic projections in the afferent auditory pathway, including connections to various subdivisions of the inferior colliculus (IC). The acoustic startle-response (ASR) is a reliable reflexive behavioral response in mammals elicited by an unexpected intense acoustic startle-eliciting stimulus (ES). It is mediated by a sub-cortical pathway that includes the IC. The ASR amplitude can be measured with an accelerometer under the subject and can be decreased in amplitude by presenting a less intense, non-startling stimulus 5–300ms before the ES. This reflexive decrement in ASR is called pre-pulse inhibition (PPI) and indicates that the relatively soft pre-pulse was heard. PPI is a general trait among mammals. Mice have been used recently to study this response and to reveal how genetic mutations affect neural circuits and hence the ASR and PPI. In this experiment, we measured the effect of Eph–ephrin mutations using control mice (C57BL/6J), mice with compromised EphA4 signaling (EphA4lacZ/+, EphA4lacZ/lacZ), and knockout ephrin-B3 mice (ephrin-B3 +/−, −/−). Control and EphA4lacZ/+strains showed robust PPI (up to 75% decrement in ASR) to an offset of a 70dB SPL background noise at 50ms before the ES. Ephrin-B3 knockout mice and EphA4 homozygous mutants were only marginally significant in PPI (<25% decrement and <33% decrement, respectively) to the same conditions. This decrement in PPI highlights the importance of ephrin-B3 and EphA4 interactions in ordering auditory behavioral circuits. Thus, different mutations in certain members of the signaling family produce a full range of changes in PPI, from minimal to nearly maximal. This technique can be easily adapted to study other aspects of hearing in a wider range of mutations. Along with ongoing neuroanatomical studies, this allows careful quantification of how the auditory anatomical, physiological and now behavioral phenotype is affected by changes in Eph–ephrin expression and functionality.

Methylmercury Exposure and Acoustic Startle Response in Adolescents: An Exploratory Study

Background The acoustic startle response (ASR) is a reflex mediated by well-described neural processes. The ASR is modified under different behavioral conditions (e.g. during attention tasks). This can be impaired in behavioral disorders, such as attention deficit disorder. Although extensively studied in animal models and some human clinical conditions, few studies have explored the use of the ASR to assess neurological effects of toxicants, and none in adolescents. Aims To describe the relationship between basic ASR amplitude, sociodemographic characteristics typically used in neurodevelopmental studies, and concurrent methylmercury (MeHg) exposure in a cohort of adolescents. Methods We report on recordings from 232 adolescents aged 8-17 years from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) study. The responses to 12 acoustic startle probes (50ms white noise bursts at ~100dB) per subject were recorded as electromyographic (EMG) activity of the eyeblink muscle. Multivariable linear regression was used to evaluate the association between concurrent MeHg exposure and demographic variables and the amplitude of the EMG activity in response to the acoustic probes (the ASR). Results Participants had a mean (SD) ASR amplitude of 1.67?V (2.09). The ASR showed expected habituation. Subject's age, maternal age at birth, socioeconomic status, mother's education, parent marital status, and smoking during pregnancy were not associated with log-transformed ASR amplitude. Sex of the child was associated with ASR amplitude: boys showed a 1.55?V (95% CI: 1.18, 2.03) smaller response than girls. Concurrent mean blood Hg concentration was 2.06 (2.22) ?g/L and was not associated with ASR magnitude. Conclusions Sex was strongly associated with ASR magnitude and will have to be carefully considered in future analyses. While concurrent blood Hg was not associated with ASR in the current analyses, we are continuing to increase our sample size, explore other mercury biomarkers, exposure windows, age ranges, and related neurological measures.

The effect of parvalbumin deficiency on the acoustic startle response and prepulse inhibition in mice

The strength of the acoustic startle response (ASR) to short bursts of broadband noise or tone pips (4, 8 and 16kHz) and the prepulse inhibition (PPI) of the ASR elicited by prepulse tones (4, 8 and 16kHz) were measured in parvalbumin-deficient (PV−/−) mice and in age-matched PV+/+ mice as controls. Hearing thresholds as determined from recordings of auditory brainstem responses were found to be similar in both genotypes. The ASRs to broadband noise and tones of low and middle frequencies were stronger than the ASRs in response to high-frequency tones in both groups. In PV−/− mice, we observed smaller ASR amplitudes in response to relatively weak startling stimuli (80–90dB sound pressure level (SPL)) of either broadband noise or 8-kHz tones compared to those recorded in PV+/+ mice. For these startling stimuli, PV−/− mice had higher ASR thresholds and longer ASR latencies. PPI of the ASR in PV−/− mice was less effective than in PV+/+ mice, for all tested prepulse frequencies (4, 8 or 16kHz) at 70dB SPL. Our findings demonstrate no effect of PV deficiency on hearing thresholds in PV−/− mice. However, the frequency-specific differences in the ASR and the significant reduction of PPI of ASR likely reflect specific changes of neuronal circuits, mainly inhibitory, in the auditory centers in PV-deficient mice.

Aggression and acoustic startle response in adult and infant rats with genetically defined aggression towards man and its absence

The aim of the current study was to investigate the association between expression of acoustic startle response and fear-induced aggression. The intensity of aggressive response towards man and acoustic startle response in adult and 15-day old Norway rats selectively bred for 70 generation for high level or the lack of fear-induced aggression was studied. Adult rats of aggressive strain demonstrated high aggression and increased amplitude of acoustic startle response compared to rats selectively bred for the lack of fear-induced aggression. It was found that, in contrast to infant rats of tame strain, 15-day old rat pups of aggressive strain demonstrated distinct aggressive response towards man, although this response was not as intensive as in adult rats of this strain. There was no considerable difference between aggressive and tame infants in amplitude of acoustic startle response. Significant habituation of startle response was shown in adult rats of aggressive strain, whereas in 15-day old rat pups of aggressive rat strain amplitude of startle response remained unaltered. Both adult and infant rats of tame strain demonstrated considerable habituation of startle response. Thus, defensive aggression in rats with genetic predisposition to fear-induced aggression appears quite early--at eyes opening they demonstrate a pronounced aggressive response toward man. The acoustic startle reflex is one of the elements of complex behavior--fear-induced aggression, and this element is involved in the enhancement of aggressive response towards man in adult rats but does not play any essential role in infant aggressiveness.

Dopaminergic mechanisms underlying involvement of the prefrontal cortex and amygdala in acoustique startle modificftion during the action of stimulus associated with positive reinforcement

We studied the neurochemical mechanisms underlying the action of the conditioned stimulus associated with positive reinforcement on the amplitude of the acoustic startle response (ASR). To this aim, we injected a blocker of dopamine D2 receptors, sulpiride, into the rat medial prefrontal cortex or basolateral amygdala during the repeated procedure of ASR habituation. We have shown that, after the injection of saline to control rats into both the prefrontal cortex and amygdala, the change in ASR amplitude after an increase in illumination depends on the preliminary learning of a behavioral skill associated with a conditioned light signal. We found that if an acoustic signal appeared immediately after the change in the illumination the blockage of D2 dopamine receptors in the medial prefrontal cortex induced an increase in ASR amplitude. This disturbed the habituation of animals that were preliminarily subjected to associative training before this procedure. The injection of sulpiride into the basolateral amygdala during the increase in illumination did not affect the dynamics of ASR amplitude. This effect of the drug did not depend on the preliminary acquirement of positive conditioning to light. Our data suggest that D2 dopamine receptors of the medial prefrontal cortex, but not the basolateral amygdala, are involved in the reproduction of previously acquired skills associated with positive reinforcement under conditions of current defensive behavior.

P03-140 - Neurotransmitters blood level, ASR prepulse modification and antisaccades deficits in schizophrenia: implication for identification of schizophrenia endophenotypes

ObjectivesStudy of psychophysiological candidate schizophrenia endophenotypes in relation with neurotransmitters blood level and mental disorders.Methods23 patients with schizophrenia and 24 healthy subjects performed horizontal antisaccades. Acoustic startle response (ASR) prepulse modification was studied according to protocol, recommended by Consortium on the genetics of schizophrenia. Neurotransmitters blood plasma level was estimated using HPLC.ResultsSignificant increase of errors and saccade latencies was revealed in patients compared to controls. ASR prepulse inhibition (PPI) at 60 ms lead interval and ASR prepulse facilitation (PPF) at 2500 ms lead interval were impaired in patients. Analysis didn’t reveal any correlations between ASR and antisaccades measures in patients while in healthy controls high initial ASR amplitude correlated with incorrect antisaccades number and PPF level correlated with antisaccades latencies. Significantly higher individual variability of plasma serotonin, glutamate and taurine content was found in patients compared to controls. Positive correlations of PPI with glutamate and taurine content were observed in patients but not in controls. At the same time, correlation between PPI and serotonine turnover ratio was positive in control group and negative in patients. Antisaccade latencies in controls displayed negative correlation with DOPAC and taurine level while in patients they positively correlated with dopamine and negatively with serotonine turnover ratio. It was also found that antisaccades parameters and ASR measures displayed correlations with different PANSS scales.ConclusionThese data support the hypothesis that PPI and antisaccades are associated with different neural networks and have different genetic aetiology.

P03-139 - The first experience of acoustic startle response prepulse modification measurement in Russian patients with schizophrenia and healthy controls

ObjectivesEstimation of acoustic startle response (ASR) and its prepulse modification in Russian population of patients with schizophrenia and healthy controls.MethodsAll subjects were males 25-50 years old. ASR was measured bilaterally by orbicularis oculi electromyographic response to 50 ms 110 dB white band noise. Prepulse at lead intervals of 60, 120 and 2500 ms were delivered according to protocol, recommended by Consortium on the genetics of schizophrenia.ResultsASR magnitude to pulse alone trials in initial block and habituation didn’t differ significantly between patients and controls. Patients compared to controls displayed reduced magnitude prepulse inhibition that was significant at 60 ms lead interval and reduction was more pronounced at the left eye. Startle latency prepulse facilitation at 60 ms lead interval was observed in patients but not in controls whereas prepulse inhibition of startle latency at 120 ms lead interval was seen in controls but not in patients. ASR amplitude prepulse facilitation (PPF) at 2500 ms lead interval was impaired in patients and this deficit was observed only in drug-naïve subjects. Effects of head trauma and experience of psychoactive drugs intake on ASR prepulse modification were revealed only in controls. High initial amplitude and short ASR latency in patients correlated with excitation level (PANSS scale P4). At the same time, PPF reduction correlated with scales P2, P4, P5, P7 and sum of positive PANSS scales.ConclusionsResults of present study testify the possibility of ASR prepulse modification use for schizophrenia endophenotyping in Russia.

Age-dependent effects of modafinil on acoustic startle and prepulse inhibition in rats

Modafinil is a psychostimulant approved for treating excessive sleepiness in adults; off-label uses (e.g., treatment of cognitive impairment in schizophrenia, ADHD and age-related dementias) are currently being explored. The effects and mechanisms of action of modafinil have not been fully established. In the present study, the effects of modafinil were examined in young adult (7-month-old) and middle-aged (21–22-month-old) rats, using the acoustic startle response (ASR) and prepulse inhibition (PPI). In the control condition, middle-aged rats showed lower activity levels, significantly lower ASR amplitudes and significantly longer ASR latencies compared to young adult rats. The effects of modafinil differed by age: activity levels and ASR amplitudes were significantly increased in middle-aged rats, whereas activity levels were lower and ASR amplitude was significantly decreased in young adult rats. Modafinil did not significantly alter PPI or startle latencies relative to the control condition. Amphetamine, used as a positive control, significantly decreased ASR amplitude in young adult rats and significantly impaired PPI for both age groups. Amphetamine-induced PPI impairment was greater for young adult rats (34% reduction in ASR amplitude) than for middle-aged rats (24% reduction). The results offer new insights into the effects of modafinil and its mechanism of action, and are consistent with the idea that modafinil enhances vigilance and cognitive functioning in individuals with deficits but not in normal, healthy individuals.