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
ABSTRACT 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. "
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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- "These data also confirm what has been reported previously for simple oddball tasks (see Hoffman and Polich, 1999) where women were found overall to have higher amplitude P350 and P450 ERP components than men. However, gender effects on behavioral responses to startle have been inconsistent with some studies finding no effects of sex (Ludewig et al., 2003), and others finding that women show less PPI compared with men (Aasen et al., 2005; Kumari et al., 2008). In the present study, although overall amplitudes were different between men and women, the difference between the amplitude of the startle compared to the prepulse/startle was not different between men and women in either the N4S or the eye blink data. "
ABSTRACT: Both physiological and behavioral studies provide evidence to suggest that deficits in frontal cortical control circuits may contribute to the risk for developing alcohol dependence. Event-related potential (ERP) and eye blink responses to startle and short delay prepulse-plus-startle stimuli, and psychiatric diagnoses were investigated in young adult (age 18-30 years) men (n=135) and women (n=205) Mexican Americans. Women displayed a significant increase in the amplitude of the eye blink response to both the startle and pre-pulse-plus-startle stimuli. None of the psychiatric diagnoses were associated with differences in eye blink responses. ERP responses to the startle and prepulse-plus startle stimuli included a negative polarity wave at approximately 400 ms that was of the highest amplitude in the frontal leads (N4S). Women were found to have significantly higher amplitude N4S responses than men. Participants with alcohol dependence demonstrated significantly less inhibition and more facilitation of the N4S component by the pre-pulse stimuli. This finding was not associated with a diagnosis of: any other drug dependence disorder (including nicotine), anxiety or affective disorder, or conduct/antisocial personality disorder. The present study suggests that gender and a lifetime diagnosis of alcohol dependence may selectively contribute to this frontal late wave electrophysiological response to prepulse-plus-startle stimuli.Psychiatry Research 07/2011; 188(2):237-44. DOI:10.1016/j.psychres.2011.04.010 · 2.47 Impact Factor
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- "Sex differences in PPF are less widely studied. Previous studies from our laboratory suggest that women show higher PPF than men (Kumari et al, 2003; Aasen et al, 2005). There is no published research to our knowledge examining menstrual cycle-related variability in PPF. "
ABSTRACT: Prepulse inhibition (PPI) of the startle response is sensitive to sex, with healthy young women showing less PPI compared with age-matched men, and varies according to the menstrual cycle phase in women. Relatively less is known regarding sex and hormonal influences in prepulse facilitation (PPF). Menstrual phase-related variability in PPI is suggested to be mediated by fluctuating estrogen level, based on the observations of more PPI in women during the follicular, relative to the luteal, phase. No study has directly assessed the relationship between fluctuating hormones and PPI or PPF levels over the human ovarian cycle. To examine the roles of circulating ovarian hormones in PPI and PPF, 16 non-smoking regularly menstruating healthy women were tested during both the follicular and luteal phases on PPI and PPF and provided saliva samples for measurement of 17beta-estradiol (estrogen), progesterone and testosterone. The results showed higher levels of 17beta-estradiol and progesterone during the luteal, relative to the follicular, phase; and more PPI during the follicular phase and more PPF during the luteal phase with comparable startle amplitude and habituation during the two phases. A larger increase in progesterone was associated with a smaller decrease in PPI from the follicular to the luteal phase. No significant associations were found between changes in PPI/PPF and estrogen levels. The findings confirm lower PPI during the luteal, compared with the follicular, phase and suggest a role for progesterone, more specifically an antipsychotic-like PPI-restoration action of progesterone, during the luteal phase in PPI of young women.Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 12/2009; 35(4):929-37. DOI:10.1038/npp.2009.195 · 7.05 Impact Factor