Patients with adverse mood effects from combined oral contraceptives have lower levels of prepulse inhibition than healthy controls

BACKGROUND: Negative mood symptoms remain one of the major reasons for discontinuation of oral contraceptive pills. The aim of this study was to compare acoustic startle response and prepulse inhibition (PPI) in women with different experience of oral contraceptive pills. METHODS: Thirty women currently on combined oral contraceptives (COCs) with no reports of adverse mood symptoms, 28 women currently on COCs and experiencing mood-related side effects from treatment, 27 women who had discontinued COC use for reasons other than adverse mood symptoms and 32 women who had discontinued COC use due to adverse mood effects were included. The eyeblink component of the acoustic startle reflex was assessed using electromyographic measurements of musculus Orbicularis Oculi. Twenty pulse-alone trials (115dB 40ms broad-band white noise) and 40 prepulse-pulse trials were presented. The prepulse stimuli consisted of a 115dB 40ms noise burst preceded at a 100ms interval by 20ms prepulses that were 72, 74, 78, or 86dB. RESULTS: Patients with adverse mood effects of COCs exhibited lower levels of PPI with 86dB prepulse compared to COC users with no adverse effects of COCs (p<0.05). There was no difference in PPI between the two groups of prior COC users. No significant difference was found between the groups regarding acoustic startle response. CONCLUSION: Relative to COC users with no reports of adverse mood symptoms, subjects suffering from COC-induced negative mood displayed deficits in PPI of acoustic startle. The fact that there was no difference in PPI between the two groups of prior COC users indicates that deficient PPI is related to adverse mood effects caused by COCs.     

Favoured genetic background for testing anxiolytics in the fear-potentiated and light-enhanced startle paradigms in the rat

The fear-potentiated startle (FPS) and the light-enhanced startle (LES) paradigms are rodent tests of fear and anxiety, which combine face validity with predictive validity for clinically effective anxiolytic drugs. However, systematic strain comparisons aimed at identifying a rat strain that shows robust and reliable fear and anxiety responses in both models are missing. Here, we investigated four commonly used laboratory rat strains: Wistar, Sprague Dawley, Long-Evans and F344. Following strong cued fear conditioning training [60 conditioned stimulus-unconditioned stimulus (CS-US) pairings], all strains except Wistar exhibited significant FPS responses. F344 rats showed the strongest FPS response. Following milder cued fear conditioning protocols, designed to reduce the underlying component of contextual fear conditioning (by context pre-exposure or less CS-US pairings), also Wistar rats were able to show significant FPS, albeit still to a lesser extent than F344 rats tested under identical conditions. When tested in the LES protocol (light intensity ∼1500 lx), all strains except Long-Evans displayed significant light-enhanced startle responses. F344 and Wistar showed the strongest LES responses, which were of similar magnitude. The most sensitive strain in both paradigms, F344, was chosen for further pharmacological validation. The clinically active anxiolytic alprazolam (0.3, 1, 3 mg/kg p.o.) dose-dependently reduced both fear-like responses in the FPS paradigm and anxiety-like responses in the LES paradigm at non-myorelaxant dosages. We propose that the F344 rat strain is particularly suited for the predictability assessment of novel anxiolytic drugs in both startle paradigms.     

Electromyographical differentiation between the acoustic blink and startle reflex. Implications for studies investigating startle behavior

Recent evidence suggests that electromyographic activity in the orbicularis oculi muscle occurring in response to sudden acoustic stimuli consists of two overlapping components: the blink and the startle reflex. The aim of the present study was to identify these two components in acoustically elicited eyeblink responses and to analyze their differential modulation by weak acoustic prepulses. The prevalence, latency and amplitude characteristics of double EMG peaks in pulse-alone and prepulse-pulse trials (PP) with 30 ms and 100 ms interstimulus intervals were assessed in 16 healthy volunteers. EMG responses with two peaks were registered in 42.6 % of the pulse-alone trials and in 56.2 % of the PP30 and 48.7 % of the PP100 trials, respectively. Prepulse inhibition of the amplitude was greater for the second peak (14.2 % (P2) vs. -11.5 % (P1) in PP30 trials; 62.6 % (P2) vs. 32.3 % (P1) in PP100 trials), resulting also in higher P1/P2 amplitude ratios in prepulse-pulse trials (P1/P2: 62.9 % in pulse-alone, 92.6 % in PP30 and 100.1 % in PP100 trials). In conclusion, double peaks are a common phenomenon in human studies of acoustically elicited blink responses. It is postulated that the first peak represents the auditory blink reflex, whereas the second peak corresponds to the startle reflex, which may be more susceptible to prepulse inhibition. This complexity should be taken into account in clinical studies of the modulation of the startle reflex. Received: 15 November 2001 / Accepted: 14 June 2002     

Lower levels of prepulse inhibition of startle response in pregnant women compared to postpartum women

OBJECTIVE: During the postpartum period, estradiol and progesterone levels decline from very high levels during late pregnancy to low levels within 48h of parturition. This period is associated with dysphoric states such as the postpartum blues. Animal studies have suggested an enhanced acoustic startle response and deficient prepulse inhibition (PPI) of startle response following progesterone withdrawal and during the postpartum period. The aim of the current study was to compare acoustic startle response and PPI in healthy third trimester pregnant women and healthy postpartum women. METHODS: Twenty-eight healthy pregnant and 21 healthy postpartum women (examined between 48h and 1 week after delivery) were recruited for the study. In addition, to evaluate the time-course of postpartum changes 11 early postpartum women (examined within 48h following delivery) were included in the study. The eyeblink component of the acoustic startle reflex was assessed using electromyographic measurements of m. Orbicularis Oculi. Twenty pulse-alone trials (115dB 40ms broad-band white noise) and 40 prepulse-pulse trials were presented. The prepulse stimuli consisted of a 115dB 40ms noise burst preceded at a 100ms interval by 20ms prepulses that were 72, 74, 78 or 86dB. RESULTS: Pregnant women exhibited lower levels of PPI compared to late postpartum women, p<0.05. There was no difference between pregnant women and postpartum women examined within 48h of delivery. There was no difference in startle response or habituation to startle response between pregnant women and either of the two groups of postpartum women. CONCLUSION: Healthy women display lower levels of PPI during late pregnancy when estradiol and progesterone levels are high compared to the late postpartum period when ovarian steroid levels have declined.     

Modulation of fear-potentiated startle and vocalizations in juvenile rhesus monkeys by morphine, diazepam, and buspirone.

BACKGROUND: Modulation of the acoustic startle response by aversive sensory stimulation is a simple and objective indicator of emotionality in rodents and human beings that has been extremely valuable for the analysis of neural systems associated with fear and anxiety. We have described a paradigm for measuring fear-potentiated, whole-body acoustic startle in nonhuman primates and have developed a protocol for maintaining fear-potentiated startle over repeated sessions with minimal extinction to allow measurement of pharmacological effects on fear-potentiated startle by using within-subjects designs in relatively small groups of monkeys. METHODS: A novel, within-subjects testing protocol was used to examine the effects of three compounds in rhesus monkeys that have anxiolytic effects in rodents on fear-potentiated startle but that differ in their mechanism of action. Spontaneous vocalizations during testing also were recorded. Juvenile monkeys that were trained to associate a visual stimulus with a fear-inducing air blast to the face were tested after acute administration of different doses of buspirone diazepam, morphine, or vehicle. RESULTS: Monkeys rapidly developed a robust and persistent elevation of startle response in the presence of the CS during repeated testing sessions. Diazepam and morphine produced dose-related reductions of fear-potentiated startle. Buspirone did not significantly reduce fear-potentiated startle at the doses tested, although a trend was evident at the highest dose. All drugs reduced rates of coo vocalizations during startle testing. CONCLUSIONS: These fear-potentiated startle results suggest that rhesus monkeys have a pharmacological profile with respect to these compounds that is closer to humans than to rats. This demonstrates the value of examining the effects of drugs on fear-potentiated startle in nonhuman primates.     

Lipopolysaccharide produces dose-dependent reductions of the acoustic startle response without impairing prepulse inhibition in male rats

This study examined the dose-dependent effects of Lipopolysaccharide (LPS) on the acoustic startle response and prepulse inhibition (PPI) in male Long-Evans rats. LPS is known to stimulate the innate immune system and result in behavior modifications referred to as "sickness behaviors". The purpose of this study was to assess the ability of LPS to modulate sensorimotor reflexes (Startle-Only trials) and/or sensory processing (PPI trials). Rats were injected intraperitoneally with LPS (50, 100 or 200 microg/kg LPS, n=9/group) or saline vehicle (n=14) on 2 test days 72 h apart. Subjects were placed in a familiar startle box apparatus where startle response magnitudes were recorded following 115 dB Startle-Only trials and PPI trials (with prepulses at +3, +6 and +12 dB above background noise). Analysis of Startle-Only trials indicated a significant dose-dependent effect of LPS on Test Day 1. The 200 microg/kg LPS group exhibited significantly reduced startle response magnitude relative to all other treatments. On the PPI trials no LPS groups displayed significantly different performance from vehicle controls. Also, DayxDrug interactions for both Startle-Only and PPI trial types indicated behavioral tolerance to LPS. LPS reduced the acoustic startle response in a dose-dependent manner on Test Day 1. From the PPI data, it is evident that all treatment groups elicited near-normal inhibition levels indicating adequate sensory function. In combination, the results suggest that the range of sickness behaviors following LPS-administration to adult rats includes decreased non-voluntary motor activity as reflected by reduced startle magnitude.     

Prepulse inhibition of acoustic startle response in mild cognitive impairment and mild dementia of Alzheimer type

Amnestic mild cognitive impairment (MCI) describes the condition of memory-impaired individuals who otherwise function well and do not meet the clinical criteria for dementia. Such individuals are considered to represent a transitional stage between normal aging and dementia of Alzheimer type (DAT). Neurobiologic changes in amnestic MCI, and their significance for psychophysiologic function, are poorly understood. In this study, the authors compared acoustic prepulse inhibition (PPI) between subjects with amnestic MCI and mild DAT to characterize sensorimotor gating. The acoustic startle reflex, which the authors measured using an accelerometer and electromyogram, involves whole-body movement and eye blink in response to a sudden loud noise (115 dB). PPI is inhibition of this reflex by a softer noise (prepulse; 85 dB) preceding the startle stimulus by 30 ms. PPI was examined in 30 controls, 20 subjects with amnestic MCI, and 20 subjects with mild DAT. Neither amnestic MCI nor mild DAT affected startle movement amplitude. Subjects with amnestic MCI showed significantly enhanced PPI (gating facilitation), while subjects with mild DAT exhibited significantly less PPI than controls (gating deficit). This pattern of PPI changes suggests that neuropathologic changes in the limbic cortex, mainly the entorhinal cortex, at the earliest stage of DAT might be responsible for PPI abnormalities via disturbed regulation of the limbic cortico-striato-pallido-pontine circuitry. Startle PPI changes could be used as a biologic marker for amnestic MCI and mild DAT.     

Individuals with Autism Spectrum Disorder Show Normal Responses to a Fear Potential Startle Paradigm

The present study utilized a fear potentiated startle paradigm to examine amygdala function in individuals with autism spectrum disorder. Two competing hypotheses regarding amygdala dysfunction in autism have been proposed: (1) The amygdala is under-responsive, in which case it would be predicted that, in a fear potentiated startle experiment, individuals with autism would exhibit decreased fear conditioning and/or potentiation, and (2) The amygdala is over responsive, in which case an exaggerated potentiation of the startle response would be predicted. Fourteen adolescents and adults diagnosed with autism spectrum disorder and 14 age, gender, IQ, and anxiety level-matched typical adolescents and adults participated. Both participants with autism and typical participants potentiated the startle response following fear conditioning and no group differences in the latency or amplitude of the potentiated startle response were found. These results suggest that this aspect of amygdala function, namely fear conditioning and potentiation of the startle response, is intact in individuals with autism.     

Effects of experimental acute tryptophan depletion on acoustic startle response in females

Previous studies suggest an important role for serotonergic (5-HT) modulation of the acoustic startle reflex (ASR) and prepulse inhibition (PPI). Acute challenge of brain serotonin by means of tryptophan depletion test (TDT) represents an established human challenge tool for temporary reduction of tryptophan (−TRP) levels and central nervous serotonin. Under these experimental conditions, PPI was found attenuated in males, but greater biochemical effects of TDT in the central nervous system of females are known. Therefore, in order to explore influence of 5-HT on various standard startle parameters in females, 16 young healthy females participated in a double-blind, cross-over TDT study. Acoustic stimuli were presented in 15 pulse-alone trials (100 dB, 40 ms) randomly followed by 25 pulse-alone or prepulse (70 dB, 30 ms; 120 ms interval) trials alongside electromyographic eyeblink recordings and mood state assessments. During 81% depletion of free plasma TRP, mean ASR magnitudes were significantly reduced compared to control (+TRP) condition while there were no differences in habituation or PPI nor did startle parameters correlate with mood states. Changes of plasma TRP and mood states correlated in tendency negatively in (−TRP) for depression and positively in (+TRP) for fatigue. In conclusion, this first study of startle parameters after TDT in a homogenous female population demonstrates that depletion of brain 5-HT in women only influences ASR.     

Phencyclidine (PCP)-induced deficits of prepulse inhibition in monkeys

Prepulse inhibition (PPI) of the acoustic startle reflex is a measure of sensorimotor gating which occurs in both rodents and humans. PPI is deficient in severe neuropsychiatric disorders such as schizophrenia. We investigated PPI in 10 adult monkeys (Cebus apella). Stimuli were 115 dB white noise startle pulses, either alone or preceded by 120 ms with a prepulse of either 8 or 16 dB above the 70 dB background noise. Experiments included a pretreatment baseline session and a session following treatment with either phencyclidine (PCP, 0.12 mg/kg, i.m.) or saline. Comparison of peak amplitudes indicated a significant intensity-dependent decrease in startle response that was similar to that observed in humans under similar experimental conditions. PCP treatment significantly disrupted PPI, but did not reduce responses to startle pulses alone. These results provide the first demonstration of PPI in monkeys. The ability of PCP to induce schizophrenia-like deficits in PPI suggests that PPI in nonhuman primates may provide an important animal model for the development of novel anti-schizophrenia medications.     

Prepulse-elicited startle in prepulse inhibition.

BACKGROUND: Prepulse inhibition (PPI) has become a major experimental paradigm in the study of psychiatric disorders. In this study, a potential confound in measurement and interpretation of PPI, namely startle reactions to so-called "nonstartling" prepulses, was examined. METHODS: Prepulses of 80, 85, and 90 dB(A) were presented on their own or followed by a pulse of 115 dB(A) (lead interval: 120 msec). RESULTS: Even at only 80 dB(A), prepulses presented alone elicited a response in about 50% of trials; and, except in the first stage of the experiment, responses became more frequent as prepulse intensity increased. Importantly, PPI at 80 and 85 dB(A) was negatively correlated with response probability to prepulses presented alone. CONCLUSIONS: Prepulses reliably activate the very startle system that they are thought to inhibit, and a high level of responsiveness to prepulses is associated with relatively lower levels of PPI. These findings might hold important implications for clinical and psychopharmacologic studies of PPI, and we suggest that the extent and influence of prepulse-elicited startles should be routinely examined.     

A single administration of testosterone reduces fear-potentiated startle in humans.

BACKGROUND: Ample evidence from animal research indicates that the gonadal steroid hormone testosterone has fear-reducing properties. Human data on this topic, however, are scarce and far less unequivocal. The present study therefore aimed to scrutinize anxiolytic effects of a single dose of testosterone, using a direct physiological index of fear in humans. METHODS: Twenty healthy female participants were tested in a double-blind, placebo-controlled crossover design involving sublingual administration of a single dose of testosterone. Four hours after intake, we assessed effects on baseline startle and fear-potentiated startle in a verbal threat-of-shock paradigm. RESULTS: In accordance with predictions, testosterone administration resulted in reduced fear-potentiated startle, without affecting baseline startle. CONCLUSIONS: This study provides direct evidence that a single dose of testosterone reduces fear in humans. The relationship of this effect to previous research on anxiolytic effects of benzodiazepines, as well as possible mechanisms of action, is discussed.     

The benzodiazepine alprazolam dissociates contextual fear from cued fear in humans as assessed by fear-potentiated startle.

BACKGROUND: The startle reflex is potentiated by aversive states. It has been proposed that phasic startle potentiation to a threat cue and sustained startle potentiation to contextual stimuli reflect distinct processes mediated by different brain structures. The present study tested the hypothesis that alprazolam would reduce the sustained startle potentiation to contextual threats but not the startle potentiation to a threat cue. METHODS: Sixteen healthy subjects received each of four treatments: placebo, .5 mg of alprazolam, 1 mg of alprazolam, and 50 mg of diphenhydramine (Benadryl) in a crossover design. Participants were exposed to three conditions, including one in which predictable aversive shocks were signaled by a cue, a second in which shocks were administered unpredictably, and a third condition in which no shocks were anticipated. Acoustic startle were delivered regularly across conditions. RESULTS: Phasic startle potentiation to the threat cue in the predictable condition was not affected by alprazolam. In contrast, the sustained increase in startle in the predictable and unpredictable conditions was reduced significantly by the high dose of alprazolam. CONCLUSIONS: Startle responses to an explicit threat cue and to an aversive context are psychopharmacologically distinct, suggesting that they may represent functionally dissociable aversive states.     

Interaction between acoustic and electric sensitization of the acoustic startle response in rats.

Sensitization is the general increase of responsiveness observed after aversive stimulation. Usually footshocks are used as aversive stimuli. According to the 'Dual Process Theory' by Groves and Thompson. Psychol. Rev. 1970;77:419-450, not only additional aversive stimuli but also the response-eliciting stimuli themselves have a sensitizing effect, the degree of sensitization depending upon the stimulus intensity. We tested this suggestion in the footshock sensitization paradigm of the acoustic startle response (ASR): (1) High SPL (sound pressure level) acoustic stimuli (119 dB SPL) presented instead of footshocks also elicited strong sensitization. (2) While footshocks presented after startle stimuli with low SPL (95 dB) were able to produce a strong further sensitization of the ASR, footshocks presented after startle stimuli with high SPL (110 dB) only caused a minor sensitization of the ASR. (3) Diazepam (3 mg/kg i.p.) decreased ASR to high SPL (115 dB) stimuli. In this case footshocks elicited significant sensitization of the ASR despite intense startle stimuli. The present results support the 'Dual Process Theory'. Furthermore we could show that acoustic and footshock sensitization interact. We therefore suggest that both, acoustic and footshock sensitization, are mediated partly via the same neural circuitry.     

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.     

Prepulse inhibition of the startle response in risperidone-treated patients: comparison with typical antipsychotics

Individuals with schizophrenia are known to show deficits in prepulse inhibition (PPI) of the startle response. PPI refers to a response suppression in reaction to a strong startling stimulus, if preceded briefly by a weak non-startling stimulus and represents a well-established animal model to investigate information processing deficits in schizophrenia. This study examined PPI of the startle acoustic response in schizophrenic patients given typical antipsychotics or a second generation atypical antipsychotic, risperidone, using a naturalistic between-subjects design. Two groups of male schizophrenic patients: (i) stable on a range of typical antipsychotics (n = 20), and (ii) stable on risperidone (n = 10) were tested for PPI (prepulse-to-pulse intervals: 30, 60, and 120 ms, prepulses 15 dB above the background) of the acoustic startle response, and compared with a group of healthy male subjects (n = 20). Patients on typical antipsychotics showed significantly less PPI with 30 and 60 ms prepulse trials than healthy subjects. Risperidone-treated patients did not differ from healthy subjects for PPI with any prepulse trials. Further longitudinal within-subject studies are now required to examine whether risperidone is superior to typical antipsychotics in improving information processing functions, as assessed by PPI of the acoustic startle response, in treatment-responsive male patients with schizophrenia.     

Pharmacogenetics,pharmacogenomics and personalized psychiatry: Are we there yet?

Previous studies suggest an important role for serotonergic (5-HT) modulation of the acoustic startle reflex (ASR) and prepulse inhibition (PPI). Acute challenge of brain serotonin by means of tryptophan depletion test (TDT) represents an established human challenge tool for temporary reduction of tryptophan (-TRP) levels and central nervous serotonin. Under these experimental conditions, PPI was found attenuated in males, but greater biochemical effects of TDT in the central nervous system of females are known. Therefore, in order to explore influence of 5-HT on various standard startle parameters in females, 16 young healthy females participated in a double-blind, cross-over TDT study. Acoustic stimuli were presented in 15 pulse-alone trials (100 dB, 40 ms) randomly followed by 25 pulse-alone or prepulse (70 dB, 30 ms; 120 ms interval) trials alongside electromyographic eyeblink recordings and mood state assessments. During 81% depletion of free plasma TRP, mean ASR magnitudes were significantly reduced compared to control (+TRP) condition while there were no differences in habituation or PPI nor did startle parameters correlate with mood states. Changes of plasma TRP and mood states correlated in tendency negatively in (-TRP) for depression and positively in (+TRP) for fatigue. In conclusion, this first study of startle parameters after TDT in a homogenous female population demonstrates that depletion of brain 5-HT in women only influences ASR.     

Exogenous testosterone attenuates the integrated central stress response in healthy young women

Animal research has shown that the androgen steroid testosterone, the end product of the hypothalamic-pituitary-gonadal (HPG) axis, down regulates the integrated stress response at multiple levels. These effects have been demonstrated at the level of the amygdala and the bed nucleus of the stria terminalis, and along the different nodes of the hypothalamic-pituitary-adrenal (HPA) axis. The present study was designed to assess effects of exogenous testosterone upon reactivity of the autonomic nervous system and modulation of the acoustic startle reflex in humans. Twenty healthy female participants received double-blind, placebo-controlled sublingual administrations of .5mg testosterone. Measurements were made of phasic electrodermal activity, cardiac responses, and startle reflexes to acoustic probes while participants were exposed to pictures with strongly aversive, neutral, or positive content. Subjective reports of mood and picture evaluations were also obtained. Results support the hypothesis of a generally decreased responsiveness of the stress system by showing reduced skin conductance responses as well as reduced affective startle modulation in anxiety-prone participants after administration of testosterone. Candidate neurobiological mechanisms of action are outlined and discussed, and it is argued that androgens promote dynamic regulation of the stress system through actions upon central neuropeptidergic pathways that control corticotropin releasing hormone (CRH) and arginine vasopressin (AVP) expression. The present findings highlight the importance of further investigation of the possible role of the HPG axis in disorders that are associated with HPA axis dysfunctions.     

Activation of a distinct arousal state immediately after spontaneous awakening from sleep

In contrast to the many neural studies into the mechanisms of sleep onset and maintenance, few studies have focused specifically on awakening from sleep. However, the abrupt electrographic changes and large brief cardio-respiratory activation at awakening suggest that a distinct, transiently aroused, awake state may exist compared to later wakefulness. To test this hypothesis we utilized the acoustic startle reflex, a standard un-conditioned reflex elicited by a sudden loud noise. This reflex is modulated under specific conditions, one being a diminution of startle when a quieter pre-stimulus is presented immediately before the loud stimulus. This pre-pulse inhibition (PPI) is used as a measure of sensorimotor gating, with smaller PPI indicating less filtering of sensory inputs and increased responsiveness to external stimuli. Eight rats with electrodes for recording sleep–wake state were studied. An accelerometer measured startle responses. The startle reflex was elicited by 115 dB, 40 ms tones. PPI was produced by 74 dB, 20 ms tones preceding the 115 dB tone by 100 ms. Responses within 100 ms were measured. Stimuli were applied either 3–10 s after spontaneous awakenings, or in established wakefulness (>30 s). Responses to the startle stimuli alone were similar in the different awake states (P=0.821). However, PPI was smaller at awakening from non-REM sleep compared to established wakefulness (45.4±7.5% vs. 74.3±6.1%, P=0.0002). PPI after awakening from REM sleep (52.8±17.9%) was not significantly different than established wakefulness (P=0.297). Reduced PPI of the startle reflex at awakening from non-REM sleep supports the hypothesis that wakefulness immediately after spontaneous sleep episodes is neurophysiologically distinct from later wakefulness and associated with reduced gating of motor responses to sensory inputs. Spontaneous activation of this distinct, transiently aroused, state upon awakening may serve a protective function, preparing an animal to respond immediately to potentially threatening stimuli.     

Rat strain-dependent effects of repeated stress on the acoustic startle response

Amplitude and habituation of the acoustic startle response were assessed in four recombinant inbred (RI) rat strains. One group from each strain underwent repeated restraint stress, the last session of which was 24h before startle testing while, a second group from each strain was not stressed prior to testing. Additionally, prepulse inhibition of the acoustic startle response, and anxiety behavior in the elevated plus-maze were assessed in separate, non-stressed groups of each strain. In the non-stressed condition, these RI strains differed significantly from each other on all behaviors measured. In the two RI strains that showed the greatest habituation of the startle response, repeated stress resulted in significantly lower acoustic startle amplitude than that seen in non-stressed controls of those strains. In the strains showing low levels of habituation, repeated stressed increased the level. Neither genotype-dependent levels of startle amplitude, prepulse inhibition of the startle response, nor anxiety in the plus-maze were closely related to the effect of stress on either startle amplitude or habituation. The results suggest that genotype-dependent habituation of the startle response may be important in determining whether stress will alter startle amplitude.