Aasen I, Kolli L, Kumari V. Sex effects in prepulse inhibition and facilitation of the acoustic startle response: implications for pharmacological and treatment studies. J Psychopharmacol 19: 39-45

Department of Psychology, Division of Psychological Medicine, Institute of Psychiatry, London, UK.
Journal of Psychopharmacology (Impact Factor: 3.59). 02/2005; 19(1):39-45. DOI: 10.1177/0269881105048890
Source: PubMed


Prepulse inhibition (PPI) refers to the reduction in the response amplitude to a startling stimuli (pulse) if it is preceded (i.e. 30-500 ms) by a weak stimulus (prepulse). If the time interval between the prepulse and pulse is more than 500 ms, then an increase in this response amplitude can be seen, termed prepulse facilitation (PPF). PPI is thought to represent an operational index of sensorimotor function whereas PPF is thought to reflect, at least to some degree, sustained attention. Interestingly, PPI is found to be sexually dimorphic, with men exhibiting more PPI than women when subjects are tested without regard to where they are in the menstrual cycle, and to be impaired in several neuropsychiatric disorders known to exhibit sex differences in their clinical presentation. PPF has received relatively less attention in both normal and clinical studies. This study examined sex differences in both PPI and PPF in 62 healthy subjects (34 women, 28 men) using a range of prepulse-to-pulse intervals to elicit PPI (30, 60, 120, 240 and 480 ms) and PPF (1000 and 2000 ms). Men showed higher PPI than women but women showed higher PPF compared to men. These results suggest that reduced PPI in healthy women is not a simple reduction but rather a shift of the inhibition/facilitation curve in the direction of facilitation in women, relative to men. Future studies investigating pharmacological and treatment effects using a prepulse modification paradigm in normal and clinical populations of both sexes would benefit from an examination of sex effects and assessments of both PPI and PPF.

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    • "This study aims to investigate whether LC neurons selectively innervate the cochlear root nucleus by determining their distribution projection pattern and neurochemical features, as well as the noradrenergic receptor subtypes in the CRNs. Interestingly, the acoustic startle reflex and its prepulse inhibition are found to be sexually dimorphic in humans and rats (Lehmann et al. 1999; Braff et al. 2001; Aasen et al. 2005). Thus, our study also aims to analyze the gene expression of adrenergic receptors in the female and male cochlear root nucleus to search for neuroanatomical evidence that might explain the gender-specific differences observed in sensory gating of the acoustic startle reflex. "
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    ABSTRACT: The cochlear root neurons (CRNs) are key components of the primary acoustic startle circuit; mediating auditory alert and escape behaviors in rats. They receive a great variety of inputs which serve to elicit and modulate the acoustic startle reflex (ASR). Recently, our group has suggested that CRNs receive inputs from the locus coeruleus (LC), a noradrenergic nucleus which participates in attention and alertness. Here, we map the efferent projection patterns of LC neurons and confirm the existence of the LC-CRN projection using both anterograde and retrograde tract tracers. Our results show that each LC projects to the CRNs of both sides with a clear ipsilateral predominance. The LC axons terminate as small endings distributed preferentially on the cell body and primary dendrites of CRNs. Using light and confocal microscopy, we show a strong immunoreactivity for tyrosine hydroxylase and dopamine β-hydroxylase in these terminals, indicating noradrenaline release. We further studied the noradrenergic system using gene expression analysis (RT-qPCR) and immunohistochemistry to detect specific noradrenergic receptor subunits in the cochlear nerve root. Our results indicate that CRNs contain a noradrenergic receptor profile sufficient to modulate the ASR, and also show important gender-specific differences in their gene expression. 3D reconstruction analysis confirms the presence of sexual dimorphism in the density and distribution of LC neurons. Our study describes a coerulean noradrenergic projection to the CRNs that might contribute to neural processes underlying sensory gating of the ASR, and also provides an explanation for the gender differences observed in the behavioral paradigm.
    Brain Structure and Function 03/2014; 220(3). DOI:10.1007/s00429-014-0739-3 · 5.62 Impact Factor
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    • "Our study has uncovered interesting differences between males and females in startle amplitudes, which support previous research. Aasen et al. (2005) reported consistently higher startle response in healthy females with no pharmacological manipulation which was also demonstrated by Kumari et al. (2004), showing that females with schizophrenia displayed greater response amplitude than affected males, reflecting the placebo results in the present study. Accordingly, an elevated baseline startle may provide more reduction potential for the startle response after dexamphetamine administration, as observed here in females. "
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    ABSTRACT: Amphetamine challenge in rodent prepulse inhibition (PPI) studies has been used to model potential dopamine involvement in effects that may be relevant to schizophrenia, though similar studies in healthy humans have failed to report replicable or robust effects. The present study investigated dexamphetamine effects on PPI in healthy humans with an increased dose and a range of startling stimulus intensities to determine participants' sensitivity and range of responses to the stimuli. A randomised, placebo-controlled dexamphetamine (0.45 mg/kg, per os.), double-blind, counterbalanced, within-subject design was used. PPI was measured in 64 participants across a range of startling stimulus intensities, during two attention set conditions (ATTEND and IGNORE). Startle magnitudes for pulse-alone and prepulse-pulse magnitudes were modelled using the startle reflex magnitude (sigmoid) function. Parameters were extracted from these fits, including the upper limit of the asymptote (maximum startle reflex capacity, R MAX), intensity threshold, stimulus intensity that elicits a half-maximal response (ES50) and the maximum rate of change of startle response magnitude to an increase in stimulus intensity. Dexamphetamine increased the threshold and ES50 of the response to pulse-alone trials in both sexes and reduced R MAX exclusively in females. Dexamphetamine modestly increased PPI of the R MAX across both attention conditions. PPI of R MAX was reduced during the ATTEND condition compared to the IGNORE condition. Results indicate that sex differences exist in motor, but not sensory, components of the startle reflex. Findings also reveal that administration of 0.45 mg/kg dexamphetamine to healthy humans does not mimic PPI effects observed in schizophrenia.
    Psychopharmacology 12/2013; 231(11). DOI:10.1007/s00213-013-3395-z · 3.88 Impact Factor
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    • "Females were not included because gender differences in the performance of the startle test could constitute a confounding variable. Indeed, it has already been found that women exhibit less startle response compared with men (Kofler et al., 2001), they show less PPI and there are also variations according to the menstrual cycle (Aasen et al., 2005; Kumari et al., 2008). Patients were excluded if they were under 18 or over 65 years of age, had a systemic or neurological disease which could interfere with coping strategies, an associated neuropsychological deficit, an IQ of under 70, or met criteria for a current major psychiatric disorder such as schizophrenia and other psychotic disorders, affective disorders, obsessive compulsive disorder and anxiety disorders, a hearing or visual impairment which might interfere with the conduct of the experiment , or a score of 15 on the Hospital Anxiety and Depression (HAD) scale (Zigmond and Snaith, 1983) as this indicates a greater likelihood of stress responses. "
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    ABSTRACT: Prepulse inhibition (PPI) of the startle reflex, which refers to the ability of innocuous sensory events to reduce the startle reflex, has been described as an operational measure of sensorimotor gating that is reduced in several neuropsychiatric disorders, such as schizophrenia, but experience is lacking in addictions and alcoholism. The aim of this study was to examine the existence of impairments in the startle response and PPI in abstinent alcoholic men. Testing for PPI was conducted on 60 abstinent alcoholic men aged 18-65 years (mean 46.37) who met DSM-IV criteria for alcohol dependence and had been abstinent for more than a month at the time of testing. The comparison group were compared with 37 sex- age- and education-matched controls without alcohol dependence. Magnitudes of the startle reflex were lower in patients than in controls. The differences were statistically significant (P < 0.05) in trials with prepulses presented 30 and 120 ms before the onset of the startle stimulus. There was also a statistically significant (P < 0.05) reduced percentage of PPI when the prepulse was presented 30 ms before the startle stimulus. These data suggest that sensory information processing mechanisms could be damaged in abstinent alcoholic patients. The fact that these findings are common to other psychiatric disorders could indicate the existence of a common vulnerability marker and explain the high degree of comorbidity between alcoholism and other mental illnesses.
    Alcohol and Alcoholism 05/2012; 47(5):545-51. DOI:10.1093/alcalc/ags055 · 2.89 Impact Factor
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